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

Phase 2

Completed

Conditions: Influenza

Interventions: Drug: Placebo
Drug: Nitazoxanide

Registration Number: NCT01227421

Lead Sponsor: Romark Laboratories L.C.

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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 624

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	2 placebo tablets twice daily for 5 days
Nitazoxanide, Placebo	Nitazoxanide	300 mg nitazoxanide tablet and 1 placebo tablet twice daily for 5 days
Nitazoxanide, Nitazoxanide	Nitazoxanide	Two 300 mg nitazoxanide tablets(600mg) twice daily for 5 days

Primary Outcome Measures

Name	Time	Method
Time to Resolution of All Clinical Symptoms of Influenza as Reported by the Subjects	Up to 28 days	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

Name	Time	Method
Mean Change (Standard Deviation)in 50% Tissue Culture Infective Dose (TCID50) Viral Titer From Baseline	7 days	Change in viral titer presented as logarithm with base 10 (log10) 50% Tissue Culture Infective Dose (TCID50)
Influenza Antibody Response: Influenza A H3N2	28 days	Change in antibody titer for Influenza A H3N2
Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects	at least 28 days	Time in hours (Median and Interquartile range)
Time to Return to Normal Daily Activities	28 days	Time in hours as reported by patient
Time Loss From Work	28 days	Time loss from work
Influenza Antibody Response: Influenza B	28 days	Change in antibody titer for Influenza B
Influenza Antibody Response: Seroprotection and Seroconversion for Influenza B	28 days	Proportion of patients seroprotected and seroconverted at day 28
Mean Change in RT-PCR (Reverse Transcription Polymerase Chain Reaction) Viral Titer From Baseline	7 days	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)	28 days	Median time in hours
Symptom Severity Score Hours	28 days	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.
Complications of Influenza	28 days	Proportion of patients with a complication of influenza during the course of the study
Influenza Antibody Response Titer Change: Influenza A 2009 H1N1	28 days	change in influenza antibody titer for Influenza A 2009 H1N1
Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A 2009 H1N1	28 days	Proportion of patients seroprotected or seroconverted at day 28
Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A H3N2	28 days	Proportion of patients seroprotected and seroconverted at day 28