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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Romark Laboratories L.C.
ClinicalTrials.gov Identifier:
NCT01227421
First received: October 21, 2010
Last updated: January 8, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Influenza
Drug: Nitazoxanide
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo Controlled Study of Nitazoxanide in Adults and Adolescents With Acute Uncomplicated Influenza

Resource links provided by NLM:


Further study details as provided by Romark Laboratories L.C.:

Primary Outcome Measures:
  • Time to Resolution of All Clinical Symptoms of Influenza as Reported by the Subjects [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
    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 Frame: at least 28 days ] [ Designated as safety issue: No ]
    Time in hours (Median and Interquartile range)

  • Mean Change (Standard Deviation)in 50% Tissue Culture Infective Dose (TCID50) Viral Titer From Baseline [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    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) [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Median time in hours

  • Time to Return to Normal Daily Activities [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Time in hours as reported by patient

  • Symptom Severity Score Hours [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    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 Frame: 28 days ] [ Designated as safety issue: No ]
    Time loss from work

  • Complications of Influenza [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Proportion of patients with a complication of influenza during the course of the study

  • Influenza Antibody Response Titer Change: Influenza A 2009 H1N1 [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    change in influenza antibody titer for Influenza A 2009 H1N1

  • Influenza Antibody Response: Influenza A H3N2 [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Change in antibody titer for Influenza A H3N2

  • Influenza Antibody Response: Influenza B [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Change in antibody titer for Influenza B

  • Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A 2009 H1N1 [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Proportion of patients seroprotected or seroconverted at day 28

  • Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A H3N2 [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Proportion of patients seroprotected and seroconverted at day 28

  • Influenza Antibody Response: Seroprotection and Seroconversion for Influenza B [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Proportion of patients seroprotected and seroconverted at day 28


Enrollment: 624
Study Start Date: December 2010
Study Completion Date: May 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Nitazoxanide, Placebo
300 mg nitazoxanide tablet and 1 placebo tablet twice daily for 5 days
Drug: Nitazoxanide
Tablets, 300 mg (one 300 mg tablet + 1 placebo tablet) with food twice daily for 5 days
Other Name: Alinia, NTZ
Active Comparator: Nitazoxanide, Nitazoxanide
Two 300 mg nitazoxanide tablets(600mg) twice daily for 5 days
Drug: Nitazoxanide
Tablets, 600 mg (two 300 mg tablets) with food twice daily for 5 days
Other Name: Alinia, NTZ
Placebo Comparator: Placebo
2 placebo tablets twice daily for 5 days
Drug: Placebo
Tablets, (2 tablets) twice daily with food for 5 days
Other Name: Sugar pill

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).

  Eligibility

Ages Eligible for Study:   12 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01227421

Locations
United States, New York
Health Sciences Research Center
Elmira, New York, United States, 14901
Sponsors and Collaborators
Romark Laboratories L.C.
Investigators
Study Director: Jean-Francois Rossignol, M.D., Ph.D. Romark Laboratories L.C.
  More Information

No publications provided by Romark Laboratories L.C.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Romark Laboratories L.C.
ClinicalTrials.gov Identifier: NCT01227421     History of Changes
Other Study ID Numbers: RM08-3001
Study First Received: October 21, 2010
Results First Received: May 30, 2012
Last Updated: January 8, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Romark Laboratories L.C.:
influenza

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
Respiratory Tract Diseases
Respiratory Tract Infections
RNA Virus Infections
Virus Diseases
Nitazoxanide
Anti-Infective Agents
Antiparasitic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014