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

Influenza Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo Controlled Study of Nitazoxanide in Adults and Adolescents With Acute Uncomplicated Influenza

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01227421
• Other study ID #: RM08-3001
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: December 2010
• Est. completion date: May 2011

Study information

• Verified date: September 2023
• Source: Romark Laboratories L.C.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 624
• Est. completion date: May 2011
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

Drug:
• Nitazoxanide
Tablets, 300 mg (one 300 mg tablet + 1 placebo tablet) with food twice daily for 5 days
• Nitazoxanide
Tablets, 600 mg (two 300 mg tablets) with food twice daily for 5 days
• Placebo
Tablets, (2 tablets) twice daily with food for 5 days

Locations

Country	Name	City	State
United States	Health Sciences Research Center	Elmira	New York

Sponsors (1)

Lead Sponsor	Collaborator
Romark Laboratories L.C.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Up to 28 days
Secondary	Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects	Time in hours (Median and Interquartile range)	at least 28 days
Secondary	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)	7 days
Secondary	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	7 days
Secondary	Time to Cessation of Viral Shedding Measure by 50% Tissue Culture Infective Dose (TCID50)	Median time in hours	28 days
Secondary	Time to Return to Normal Daily Activities	Time in hours as reported by patient	28 days
Secondary	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.	28 days
Secondary	Time Loss From Work	Time loss from work	28 days
Secondary	Complications of Influenza	Proportion of patients with a complication of influenza during the course of the study	28 days
Secondary	Influenza Antibody Response Titer Change: Influenza A 2009 H1N1	change in influenza antibody titer for Influenza A 2009 H1N1	28 days
Secondary	Influenza Antibody Response: Influenza A H3N2	Change in antibody titer for Influenza A H3N2	28 days
Secondary	Influenza Antibody Response: Influenza B	Change in antibody titer for Influenza B	28 days
Secondary	Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A 2009 H1N1	Proportion of patients seroprotected or seroconverted at day 28	28 days
Secondary	Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A H3N2	Proportion of patients seroprotected and seroconverted at day 28	28 days
Secondary	Influenza Antibody Response: Seroprotection and Seroconversion for Influenza B	Proportion of patients seroprotected and seroconverted at day 28	28 days