A Phase III, Randomized, Double-Blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Nitazoxanide in the Treatment of Uncomplicated Influenza

Influenza Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03336619
• Other study ID #: RM08-3004
• Status: Completed
• Phase: Phase 3
• Start date: January 17, 2018
• Est. completion date: April 17, 2019

Study information

• Verified date: April 2022
• Source: Romark Laboratories L.C.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1030
• Est. completion date: April 17, 2019
• Est. primary completion date: April 17, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

Drug:
• Nitazoxanide
Nitazoxanide 600 mg administered orally twice daily for five days
• Placebo
Placebo administered orally twice daily for five days

Locations

Country	Name	City	State
Australia	Vanguard Study Site	Morayfield	Queensland
Australia	Vanguard Study Site	Sherwood	Queensland
Australia	Vanguard Study Site	Victoria Point	Queensland
Puerto Rico	Vanguard Study Site	Ponce
United States	Vanguard Study Site	Alabaster	Alabama
United States	Vanguard Study Site	Anaheim	California
United States	Vanguard Study Site	Austin	Texas
United States	Vanguard Study Site	Birmingham	Alabama
United States	Vanguard Study Site	Birmingham	Alabama
United States	Vanguard Study Site	Brooklyn	New York
United States	Vanguard Study Site	Carrollton	Texas
United States	Vanguard Study Site	Cincinnati	Ohio
United States	Vanguard Study Site	Columbus	Ohio
United States	Vanguard Study Site	Dallas	Texas
United States	Vanguard Study Site	Dallas	Texas
United States	Vanguard Study Site	Dayton	Ohio
United States	Vanguard Study Site	Fort Worth	Texas
United States	Vanguard Study Site	Goodyear	Arizona
United States	Vanguard Study Site	Hoover	Alabama
United States	Vanguard Study Site	Hot Springs	Arkansas
United States	Vanguard Study Site	Houston	Texas
United States	Vanguard Study Site	Jackson	Tennessee
United States	Vanguard Study Site	Lauderdale Lakes	Florida
United States	Vanguard Study Site	Medford	Oregon
United States	Vanguard Study Site	Missoula	Montana
United States	Vanguard Study Site	New Orleans	Louisiana
United States	Vanguard Study Site	Orlando	Florida
United States	Vanguard Study Site	Pelham	Alabama
United States	Vanguard Study Site	Pharr	Texas
United States	Vanguard Study Site	Plano	Texas
United States	Vanguard Study Site	Plano	Texas
United States	Vanguard Study Site	Rapid City	South Dakota
United States	Vanguard Study Site	Saint George	Utah
United States	Vanguard Study Site	Saint Louis	Missouri
United States	Vanguard Study Site	Smyrna	Tennessee
United States	Vanguard Study Site	Tolleson	Arizona
United States	Vanguard Study Site	Valparaiso	Indiana
United States	Vanguard Study Site	Westminster	California

Sponsors (1)

Lead Sponsor	Collaborator
Romark Laboratories L.C.

Countries where clinical trial is conducted

United States,  Australia,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Time to Return to Usual Health	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.	21 days
Other	Proportion of Diaries Misclassified by Novel Response Definition	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.	21 days
Primary	Time From First Dose to Symptom Response	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	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
Secondary	Number of Subjects Experiencing One or More Complications of Influenza	Complications of influenza infection included pneumonia, otitis media, bronchitis, sinusitis, worsening of pre-existing health conditions, systemic antibiotic use for infections secondary to influenza infection, hospitalization due to influenza or complications of influenza and death.	Up to 21 days
Secondary	Time to Symptom Response Excluding the FLU-PRO Gastrointestinal and Eye Domains	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 25 FLU-PRO symptoms (excluding gastrointestinal and eye 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 25 symptom thresholds most closely associated with patient-reported usual health.	Up to 21 days