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

NCT03336619 | Completed Phase 3 Results FDA Drug

• 1 other identifier: RM08-3004
• Study Type: interventional
• Target: 1,030
• Locations: 3 countries
• Sites: 38

Brief Summary

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

Conditions

Influenza

Keywords

Influenza

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Time From First Dose to Ability to Perform All Normal Activities

  Up to 21 days

• Number of Subjects Experiencing One or More Complications of Influenza

  Up to 21 days

• Time to Symptom Response Excluding the FLU-PRO Gastrointestinal and Eye Domains

  Up to 21 days

Other Outcomes (2)

• Time to Return to Usual Health

  21 days

• Proportion of Diaries Misclassified by Novel Response Definition

  21 days

Study Arms (2)

Nitazoxanide

ACTIVE COMPARATOR

Two Nitazoxanide 300 mg tablets orally twice daily (b.i.d.) for 5 days

Drug: Nitazoxanide

Placebo

PLACEBO COMPARATOR

Two Placebo tablets orally twice daily (b.i.d.) for 5 days

Drug: Placebo

Interventions

Nitazoxanide DRUG

Nitazoxanide 600 mg administered orally twice daily for five days

Also known as: NTZ, NT-300

Nitazoxanide

Placebo DRUG

Placebo administered orally twice daily for five days

Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects at least 12 years of age
• Presence of clinical signs and/or symptoms consistent with an acute illness compatible with influenza infection (each of the following is required):
• 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
• at least one of the following respiratory symptoms (cough, sore throat, nasal obstruction), AND
• one of the following constitutional symptoms (fatigue, headache, myalgia, feverishness).
• Confirmation of influenza A or B infection in the local community by one of the following means:
• the institution's local laboratory,
• the local public health system,
• the national public health system, OR
• a laboratory of a recognized national or multinational influenza surveillance scheme.
• 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:
• the time when the temperature was first measured as elevated, OR
• the time when the subject experienced the presence of at least one respiratory symptom AND the presence of at least one constitutional symptom.
• 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.

You may not qualify if:

• Severity of illness requiring or anticipated to require in-hospital care.
• Moderate or severe persistent asthma.
• Cystic fibrosis in children.
• Stage III or IV (severe or very severe) chronic obstructive pulmonary disease (COPD).
• 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)
• Arrhythmia
• Immunosuppressive disorders or who are receiving immunosuppressive therapy (e.g., for organ or bone marrow transplants)
• 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%)
• Residents of any age of nursing homes or other long-term care institutions
• Concurrent infection at the screening examination that requires systemic antimicrobial therapy.
• Receipt of any dose of NTZ, oseltamivir, zanamivir, peramivir, laninamivir, baloxavir, amantadine or rimantadine within 3 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.

Sponsors & Collaborators

• Romark Laboratories L.C.: lead

Study Sites (38)

Vanguard Study Site

Alabaster, Alabama, 35007, United States

Location

Vanguard Study Site

Birmingham, Alabama, 35235, United States

Location

Vanguard Study Site

Birmingham, Alabama, 35242, United States

Location

Vanguard Study Site

Hoover, Alabama, 35216, United States

Location

Vanguard Study Site

Pelham, Alabama, 35124, United States

Location

Vanguard Study Site

Goodyear, Arizona, 85338, United States

Location

Vanguard Study Site

Tolleson, Arizona, 85353, United States

Location

Vanguard Study Site

Hot Springs, Arkansas, 71913, United States

Location

Vanguard Study Site

Anaheim, California, 92805, United States

Location

Vanguard Study Site

Westminster, California, 92683, United States

Location

Vanguard Study Site

Lauderdale Lakes, Florida, 33319, United States

Location

Vanguard Study Site

Orlando, Florida, 32806, United States

Location

Vanguard Study Site

Valparaiso, Indiana, 46383, United States

Location

Vanguard Study Site

New Orleans, Louisiana, 70124, United States

Location

Vanguard Study Site

St Louis, Missouri, 63141, United States

Location

Vanguard Study Site

Missoula, Montana, 59808, United States

Location

Vanguard Study Site

Brooklyn, New York, 11229, United States

Location

Vanguard Study Site

Cincinnati, Ohio, 45215, United States

Location

Vanguard Study Site

Columbus, Ohio, 43214, United States

Location

Vanguard Study Site

Dayton, Ohio, 45424, United States

Location

Vanguard Study Site

Medford, Oregon, 97504, United States

Location

Vanguard Study Site

Rapid City, South Dakota, 57702, United States

Location

Vanguard Study Site

Jackson, Tennessee, 38305, United States

Location

Vanguard Study Site

Smyrna, Tennessee, 37167, United States

Location

Vanguard Study Site

Austin, Texas, 78735, United States

Location

Vanguard Study Site

Carrollton, Texas, 75010, United States

Location

Vanguard Study Site

Dallas, Texas, 75204, United States

Location

Vanguard Study Site

Dallas, Texas, 75230, United States

Location

Vanguard Study Site

Fort Worth, Texas, 76107, United States

Location

Vanguard Study Site

Houston, Texas, 77058, United States

Location

Vanguard Study Site

Pharr, Texas, 78577, United States

Location

Vanguard Study Site

Plano, Texas, 75024, United States

Location

Vanguard Study Site

Plano, Texas, 75093, United States

Location

Vanguard Study Site

St. George, Utah, 84790, United States

Location

Vanguard Study Site

Morayfield, Queensland, 4506, Australia

Location

Vanguard Study Site

Sherwood, Queensland, 4075, Australia

Location

Vanguard Study Site

Victoria Point, Queensland, 4165, Australia

Location

Vanguard Study Site

Ponce, 00780, Puerto Rico

Location

MeSH Terms

Conditions

Influenza, Human

Interventions

nitazoxanide

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Limitations and Caveats

Limitations of this study include inability to establish meaningfulness of the novel primary endpoint and selection of patients for whom the benefit of antiviral therapy may be marginal (e.g., vaccinated, antibody-positive, and subjects with improving illness at Baseline).

Results Point of Contact

• Title: Sr. Director, Research Operations
• Organization: Romark

jessica.fulgencio@romark.com

8132828544

Study Officials

• Jean-Francois Rossignol, M.D., Ph.D.

  Romark Laboratories L.C.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2017
• First Posted: November 8, 2017
• Study Start: January 17, 2018
• Primary Completion: April 17, 2019
• Study Completion: April 17, 2019
• Last Updated: June 28, 2022
• Results First Posted: June 28, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

PR (1); AU (3); US (34)