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Safety and Efficacy Study of Nitazoxanide in the Treatment of Acute Uncomplicated Influenza

Primary Purpose

Influenza

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Nitazoxanide
Nitazoxanide
Placebo
Sponsored by
Romark Laboratories L.C.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Influenza focused on measuring influenza

Eligibility Criteria

12 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

INCLUSION CRITERIA

  • age 12 to 65 years

  • Presence of clinical signs, respiratory symptoms and constitutional symptoms compatible with influenza infection:

    1. fever,
    2. at least one of the following respiratory symptoms: cough, sore throat, nasal discharge, nasal congestion, sneezing.
    3. At least one of the following constitutional symptoms: headache, myalgia, seats, chills, fatigue of any severity (mild, moderate, severe)
  • Confirmation of Influenza A or B infection in the local community
  • Onset of illness no more than 48 hours before presentation. 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 patient experienced the presence of at least one respiratory symptom AND the presence of at least one constitutional symptom.
  • willing and able to comply with protocol requirements and provide informed consent

EXCLUSION CRITERIA:

  • severity of illness requiring or anticipated to require in-hospital care

  • High risk of complications from influenza as follows:

    1. persons with asthma or other chronic pulmonary diseases
    2. persons with hemodynamically significant cardiac disease
    3. persons who have immunosuppressive disorders or receiving immunosuppressive therapy
    4. persons infected with Human Immunodeficiency Virus (HIV)
    5. persons with sickle cell anemia or other hemoglobinopathies
    6. persons with diseases requiring long-term aspirin therapy
    7. persons with chronic renal dysfunction
    8. persons with liver disorders
    9. Persons with cancer
    10. Persons with chronic metabolic disease such as diabetes and inherited mitochondrial disorders
    11. Persons with neuromuscular disorders, seizure disorders, or cognitive dysfunction
    12. Residents of any age of nursing homes or long-term institutions.
  • Females of child bearing age who are pregnant, breastfeeding or sexually active without birth control
  • vaccination for influenza or H1N1 (Swine Flu) on or after August 1, 2010
  • treatment with antiviral medication such as oseltamivir, zanamivir, amantadine, or rimantadine within 30 days of screening.
  • Prior treatment with nitazoxanide within 30 days prior to screening.
  • subjects with active respiratory allergies or expected to require anti-allergy medications during the study period.
  • known sensitivity to nitazoxanide
  • subjects unable to take oral medication
  • subjects with chronic kidney or liver disease
  • Presence of any other pre-existing chronic infection that is undergoing or requiring medical therapy

Sites / Locations

  • Health Sciences Research Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Placebo Comparator

Arm Label

Nitazoxanide, Placebo

Nitazoxanide, Nitazoxanide

Placebo

Arm Description

300 mg nitazoxanide tablet and 1 placebo tablet twice daily for 5 days

Two 300 mg nitazoxanide tablets(600mg) twice daily for 5 days

2 placebo tablets twice daily for 5 days

Outcomes

Primary Outcome Measures

Time to Resolution of All Clinical Symptoms of Influenza as Reported by the Subjects
The primary efficacy analysis for this study was to demonstrate the efficacy of Nitazoxanide (NTZ) administered as 300 mg b.i.d. for 5 days or 600 mg b.i.d. for 5 days in reducing the time to resolution of all clinical symptoms of influenza in patients with laboratory confirmed influenza infection

Secondary Outcome Measures

Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects
Time in hours (Median and Interquartile range)
Mean Change (Standard Deviation)in 50% Tissue Culture Infective Dose (TCID50) Viral Titer From Baseline
Change in viral titer presented as logarithm with base 10 (log10) 50% Tissue Culture Infective Dose (TCID50)
Mean Change in RT-PCR (Reverse Transcription Polymerase Chain Reaction) Viral Titer From Baseline
Change in viral titer logarithm with base 10 (log10) Ribonucleic Acid (RNA)copies
Time to Cessation of Viral Shedding Measure by 50% Tissue Culture Infective Dose (TCID50)
Median time in hours
Time to Return to Normal Daily Activities
Time in hours as reported by patient
Symptom Severity Score Hours
Sum of the symptom severity score hours from first dose to resolution of symptoms. Patients rated each symptom's severity on a score from 0 to 3 (0=absent, 1=mild, 2=moderate, 3=severe). Total symptom severity score hours were calculated by multiplying the sum of the severity scores by duration of symptoms.
Time Loss From Work
Time loss from work
Complications of Influenza
Proportion of patients with a complication of influenza during the course of the study
Influenza Antibody Response Titer Change: Influenza A 2009 H1N1
change in influenza antibody titer for Influenza A 2009 H1N1
Influenza Antibody Response: Influenza A H3N2
Change in antibody titer for Influenza A H3N2
Influenza Antibody Response: Influenza B
Change in antibody titer for Influenza B
Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A 2009 H1N1
Proportion of patients seroprotected or seroconverted at day 28
Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A H3N2
Proportion of patients seroprotected and seroconverted at day 28
Influenza Antibody Response: Seroprotection and Seroconversion for Influenza B
Proportion of patients seroprotected and seroconverted at day 28

Full Information

First Posted
October 21, 2010
Last Updated
September 28, 2023
Sponsor
Romark Laboratories L.C.
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1. Study Identification

Unique Protocol Identification Number
NCT01227421
Brief Title
Safety and Efficacy Study of Nitazoxanide in the Treatment of Acute Uncomplicated Influenza
Official Title
A Randomized, Double-Blind, Placebo Controlled Study of Nitazoxanide in Adults and Adolescents With Acute Uncomplicated Influenza
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
December 2010 (undefined)
Primary Completion Date
April 2011 (Actual)
Study Completion Date
May 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Romark Laboratories L.C.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a randomized clinical trial designed to evaluate the safety/efficacy of two dosing regimens of oral nitazoxanide compared to placebo in the treatment of acute uncomplicated influenza in adults and adolescents. The investigators hypothesize that treatment with Nitazoxanide will reduce the duration of symptoms in patients with confirmed influenza infection. Secondarily, the investigators hypothesize that treatment with nitazoxanide will reduce the complications of influenza, severity of symptoms, time lost from work, time to return to normal daily activities.
Detailed Description
A Randomized, Double-Blind, Placebo Controlled Study of Nitazoxanide in Adults and Adolescents with Acute Uncomplicated Influenza. The primary objectives of this study are to demonstrate the efficacy of nitazoxanide administered 300 mg two times per day for 5 days or 600 mg two times per day for 5 days in reducing the time to resolution of all clinical symptoms of influenza. The study will also evaluate pharmacokinetics of nitazoxanide in a subset of 24 patients and the safety of the nitazoxanide regimen compared to a placebo via analysis of adverse events and laboratory safety tests. Blood samples will be collected for all patients at baseline, day 7 and day 28, and for a subset of 24 patients aged 18-65 years (pharmacokinetics subset) on day 2. Urine samples will be collected at baseline and day 7. Nasal swabs will be collected at baseline and day 7 for all patients and on days 2, 3, 4 and 5 for a subset of patients (approximately 20% of patients).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza
Keywords
influenza

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
624 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Nitazoxanide, Placebo
Arm Type
Active Comparator
Arm Description
300 mg nitazoxanide tablet and 1 placebo tablet twice daily for 5 days
Arm Title
Nitazoxanide, Nitazoxanide
Arm Type
Active Comparator
Arm Description
Two 300 mg nitazoxanide tablets(600mg) twice daily for 5 days
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
2 placebo tablets twice daily for 5 days
Intervention Type
Drug
Intervention Name(s)
Nitazoxanide
Other Intervention Name(s)
Alinia, NTZ
Intervention Description
Tablets, 300 mg (one 300 mg tablet + 1 placebo tablet) with food twice daily for 5 days
Intervention Type
Drug
Intervention Name(s)
Nitazoxanide
Other Intervention Name(s)
Alinia, NTZ
Intervention Description
Tablets, 600 mg (two 300 mg tablets) with food twice daily for 5 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Sugar pill
Intervention Description
Tablets, (2 tablets) twice daily with food for 5 days
Primary Outcome Measure Information:
Title
Time to Resolution of All Clinical Symptoms of Influenza as Reported by the Subjects
Description
The primary efficacy analysis for this study was to demonstrate the efficacy of Nitazoxanide (NTZ) administered as 300 mg b.i.d. for 5 days or 600 mg b.i.d. for 5 days in reducing the time to resolution of all clinical symptoms of influenza in patients with laboratory confirmed influenza infection
Time Frame
Up to 28 days
Secondary Outcome Measure Information:
Title
Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects
Description
Time in hours (Median and Interquartile range)
Time Frame
at least 28 days
Title
Mean Change (Standard Deviation)in 50% Tissue Culture Infective Dose (TCID50) Viral Titer From Baseline
Description
Change in viral titer presented as logarithm with base 10 (log10) 50% Tissue Culture Infective Dose (TCID50)
Time Frame
7 days
Title
Mean Change in RT-PCR (Reverse Transcription Polymerase Chain Reaction) Viral Titer From Baseline
Description
Change in viral titer logarithm with base 10 (log10) Ribonucleic Acid (RNA)copies
Time Frame
7 days
Title
Time to Cessation of Viral Shedding Measure by 50% Tissue Culture Infective Dose (TCID50)
Description
Median time in hours
Time Frame
28 days
Title
Time to Return to Normal Daily Activities
Description
Time in hours as reported by patient
Time Frame
28 days
Title
Symptom Severity Score Hours
Description
Sum of the symptom severity score hours from first dose to resolution of symptoms. Patients rated each symptom's severity on a score from 0 to 3 (0=absent, 1=mild, 2=moderate, 3=severe). Total symptom severity score hours were calculated by multiplying the sum of the severity scores by duration of symptoms.
Time Frame
28 days
Title
Time Loss From Work
Description
Time loss from work
Time Frame
28 days
Title
Complications of Influenza
Description
Proportion of patients with a complication of influenza during the course of the study
Time Frame
28 days
Title
Influenza Antibody Response Titer Change: Influenza A 2009 H1N1
Description
change in influenza antibody titer for Influenza A 2009 H1N1
Time Frame
28 days
Title
Influenza Antibody Response: Influenza A H3N2
Description
Change in antibody titer for Influenza A H3N2
Time Frame
28 days
Title
Influenza Antibody Response: Influenza B
Description
Change in antibody titer for Influenza B
Time Frame
28 days
Title
Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A 2009 H1N1
Description
Proportion of patients seroprotected or seroconverted at day 28
Time Frame
28 days
Title
Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A H3N2
Description
Proportion of patients seroprotected and seroconverted at day 28
Time Frame
28 days
Title
Influenza Antibody Response: Seroprotection and Seroconversion for Influenza B
Description
Proportion of patients seroprotected and seroconverted at day 28
Time Frame
28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA age 12 to 65 years Presence of clinical signs, respiratory symptoms and constitutional symptoms compatible with influenza infection: fever, at least one of the following respiratory symptoms: cough, sore throat, nasal discharge, nasal congestion, sneezing. At least one of the following constitutional symptoms: headache, myalgia, seats, chills, fatigue of any severity (mild, moderate, severe) Confirmation of Influenza A or B infection in the local community Onset of illness no more than 48 hours before presentation. 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 patient experienced the presence of at least one respiratory symptom AND the presence of at least one constitutional symptom. willing and able to comply with protocol requirements and provide informed consent EXCLUSION CRITERIA: severity of illness requiring or anticipated to require in-hospital care High risk of complications from influenza as follows: persons with asthma or other chronic pulmonary diseases persons with hemodynamically significant cardiac disease persons who have immunosuppressive disorders or receiving immunosuppressive therapy persons infected with Human Immunodeficiency Virus (HIV) persons with sickle cell anemia or other hemoglobinopathies persons with diseases requiring long-term aspirin therapy persons with chronic renal dysfunction persons with liver disorders Persons with cancer Persons with chronic metabolic disease such as diabetes and inherited mitochondrial disorders Persons with neuromuscular disorders, seizure disorders, or cognitive dysfunction Residents of any age of nursing homes or long-term institutions. Females of child bearing age who are pregnant, breastfeeding or sexually active without birth control vaccination for influenza or H1N1 (Swine Flu) on or after August 1, 2010 treatment with antiviral medication such as oseltamivir, zanamivir, amantadine, or rimantadine within 30 days of screening. Prior treatment with nitazoxanide within 30 days prior to screening. subjects with active respiratory allergies or expected to require anti-allergy medications during the study period. known sensitivity to nitazoxanide subjects unable to take oral medication subjects with chronic kidney or liver disease Presence of any other pre-existing chronic infection that is undergoing or requiring medical therapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean-Francois Rossignol, M.D., Ph.D.
Organizational Affiliation
Romark Laboratories L.C.
Official's Role
Study Director
Facility Information:
Facility Name
Health Sciences Research Center
City
Elmira
State/Province
New York
ZIP/Postal Code
14901
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24852376
Citation
Haffizulla J, Hartman A, Hoppers M, Resnick H, Samudrala S, Ginocchio C, Bardin M, Rossignol JF; US Nitazoxanide Influenza Clinical Study Group. Effect of nitazoxanide in adults and adolescents with acute uncomplicated influenza: a double-blind, randomised, placebo-controlled, phase 2b/3 trial. Lancet Infect Dis. 2014 Jul;14(7):609-18. doi: 10.1016/S1473-3099(14)70717-0. Epub 2014 May 19.
Results Reference
derived

Learn more about this trial

Safety and Efficacy Study of Nitazoxanide in the Treatment of Acute Uncomplicated Influenza

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