Phase 3 Efficacy and Safety Study of Favipiravir for Treatment of Uncomplicated Influenza in Adults - T705US316

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine if favipiravir is effective in reducing the time to resolution of influenza symptoms.

Detailed Description
-----------------
The purpose of this study is to determine if a 5-day regimen of favipiravir reduces the time to alleviation of influenza symptoms, resolution of fever, and viral shedding, in subjects with uncomplicated influenza compared to no treatment (e.g. placebo).

Official Title
-----------------
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Evaluating the Efficacy and Safety of Favipiravir in Adult Subjects With Uncomplicated Influenza (T705US316)

Conditions
-----------------
Influenza

Intervention / Treatment
-----------------
* Drug: favipiravir
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: At time of enrollment has 2 or more of the following symptoms (moderate to severe in intensity) that began 48 hours or less prior to the anticipated start of dosing with study medication: cough, sore throat, headache, nasal congestion, body aches and pains, fatigue Has a fever at the first visit or in the 6 hours prior if antipyretics were taken, defined as: ≥ 38.0°C (≥ 100.4°F) if < 65 years old; or ≥ 37.8°C (≥ 100.0°F) if ≥ 65 years old Tests positive for influenza A or B during the 48 hours between onset of symptoms and anticipated dosing with study medication as confirmed by RAT or PCR testing (study or non-study procedure); or per Investigator and Medical Monitor discretion in the event there is a known influenza outbreak circulating in the community or the subject has been in close contact with a person who was recently confirmed to have laboratory-confirmed influenza Willing to adhere to strict contraceptive measures throughout study and for 3 months following last dose of study medication Exclusion Criteria: Female subjects who are pregnant, currently breast-feeding, or have a positive pregnancy test at Screening Has taken an anti-influenza drug, or received any live attenuated influenza vaccine within 4 weeks prior to signing the informed consent Has underlying chronic respiratory disease; includes bronchial asthma if currently experience asthma symptoms, requires current asthma treatment, or has had an asthma attack in the past year Is suspected of having bacterial respiratory infection (i.e., expectoration of purulent or mucopurulent sputum and/or infiltrate in lung observed on chest x ray, or is on antibiotics for pulmonary disease) at start of study Has a history of gout or is under treatment for: gout or hyperuricemia; hereditary xanthinuria; hypouricemia or xanthine calculi of the urinary tract Has a history of hypersensitivity to an anti-viral nucleoside-analog drug targeting a viral RNA polymerase Current use of adrenocorticosteroids (except topical preparation) or immunosuppressive drugs Has an allergy or contraindication to use of acetaminophen (paracetamol) Has a serious chronic disease, history of alcohol or drug abuse within preceding 2 years, psychiatric illness not well controlled (not on stable regimen > 1 year), or is deemed by the Investigator to be ineligible for any reason Previously participated in a clinical trial of favipiravir (T-705) Has renal insufficiency requiring hemodialysis or continuous ambulatory peritoneal dialysis (CAPD)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: favipiravir<br> | Drug: favipiravir<br>* Administered twice daily over 5 consecutive days for a total of 10 doses. Day 1: 1800 mg twice daily (loading doses) Days 2 through 5: 800 mg twice daily<br>* Other names: T-705;|
| Placebo Comparator: placebo<br> | Drug: Placebo<br>* Administered twice daily over 5 consecutive days for a total of 10 doses.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to alleviation of all primary influenza symptoms and fever | Time from the start of study treatment until alleviation of all primary influenza symptoms (i.e. cough, sore throat, headache, nasal congestion, body aches and pains, fatigue) and to resolution of fever. Subjects will be considered to have symptoms alleviated if individual symptoms are no greater than mild and are confirmed to be no greater than mild at least 21.5 hours later. Similarly, resolution of fever is defined as temperature (oral) measurements to be < 38.0°C (<100.4°F) for subjects < 65 years old and < 37.8°C (100.0°F) for subjects ≥ 65 years old, and measurements are confirmed at least 21.5 hours later. For the primary endpoint, the time periods of alleviation/fever resolution must be concurrent for symptoms and temperature. | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to alleviation each of the primary influenza symptoms and fever | Time from the start of study treatment until alleviation of each of the following influenza symptoms (cough, sore throat, headache, nasal congestion, body aches and pains, and fatigue) and to resolution of fever. Subjects will be considered to have symptoms alleviated if individual symptoms are no greater than mild and are confirmed to be no greater than mild at least 21.5 hours later. Similarly, resolution of fever is defined as temperature (oral) measurements to be < 38.0°C (<100.4°F) for subjects < 65 years old and < 37.8°C (100.0°F) for subjects ≥ 65 years old, and measurements are confirmed at least 21.5 hours later. Additional analyses of symptoms, including assessment of the impact of relevant covariates, will be specified in the Statistical Analysis Plan. | 21 days | 
| To characterize the PK of favipiravir when used under clinical conditions | Population PK analysis of favipiravir with assessment of maximum plasma concentration (Cmax), minimum plasma concentration (Cmin), and total daily exposure AUC(0-24h) on Visits 1, 2, 3, 4 and 5 | 21 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
influenza, flu, fever, cough, body aches, headache, nasal congestion, body pains, sore throat, fatigue, T-705, favipiravir, favor, flu symptoms