T-705a Multicenter Study in Adults Subjects With Uncomplicated Influenza

Study Overview
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Brief Summary
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This is safety and pharmacokinetics (PK) of favipiravir study in adults 18-80 years of age diagnosed with uncomplicated influenza.

Official Title
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Randomized, Double Blind,Placebo-Controlled, Multicenter Study Evaluating the Safety and Pharmacokinetics of Different Dosing Regimens of Favipiravir in Healthy Adult Subjects and Adult Subjects With Uncomplicated Influenza

Conditions
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Influenza

Intervention / Treatment
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* Drug: Placebo
* Drug: Favipiravir
* Drug: Favipiravir
* Drug: Favipiravir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Understand the requirements of the study and has provided written informed consent prior to undergoing any study-related procedures. Is male or female between the ages of 18 and 80 years old, inclusive. Tests positive for influenza A or B by a commercially available Rapid Antigen Test (RAT) -OR- Has influenza confirmed by diagnostic assay (e.g. non-study RAT or PCR) from another clinic during the 48 hours between onset of symptoms and anticipated dosing. (Note: A subject with a negative RAT result may still enroll if the Medical Monitor and Investigator agree that 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 influenza by RAT or another lab test). Has a fever, defined for subjects ≥18 but ≤65 years old as a temperature (oral) of 100.4°F (38.0°C) or more; subjects >65 years old with a temperature (oral) of 100.0°F (37.8°C) or more at the first visit or in the 6 hours prior if antipyretics were taken before the visit. If male, subject must: a. Be sterile (have had a vasectomy at least 6 months prior to Day 1 dosing and had sperm counts verifying that he is no longer fertile) OR b. Agree he will not donate sperm during the study and for 3 months following the last dose of study medication, and c. Will strictly adhere to the following contraceptive measures for 3 months after the last dose of study medication: i. Abstain from sexual intercourse or; ii. Use a condom during sexual intercourse with a female of child-bearing potential. In addition to the male condom, the female partner must use another form of contraception (e.g. intrauterine device (IUD), diaphragm with spermicide, oral contraceptives, injectable progesterone, or subdermal implants) for at least 3 months following Day 1 dosing). If female, subject must: a. Be unable to bear children (have not had a period for ≥12 consecutive months, have had her uterus or ovaries removed, or have had a tubal ligation) OR b. Have a male partner incapable of fathering a child (has had a vasectomy at least 6 months prior to study entry and has had sperm counts verifying that he is no longer fertile) OR c. Have a negative urine pregnancy test at screening AND d. Not have had unprotected sex within the last month AND e. If she is of childbearing potential, will strictly adhere to the following contraceptive measures during the study and for 3 months following the last dose of study medication: i. Abstain from sexual intercourse or ii. Her male partner agrees to use a condom during sexual intercourse AND iii. She agrees to use an approved method of contraception (e.g., IUD, diaphragm with spermicide, oral contraceptives, injectable progesterone, or subdermal implants). Has 2 or more of the following symptoms (moderate to severe in intensity) at the time of enrollment that began 48 hours or less prior to first dose: Cough Sore throat Headache Nasal congestion Body aches and pains Fatigue Influenza Symptom Intensity: 0: None Mild, Symptoms are tolerable, possible to perform daily activities Moderate, Symptoms are disturbing, partially interfere with daily activities Severe, Symptoms are intolerable, impossible to perform daily activities Exclusion Criteria: Has taken an anti-influenza drug (e.g., amantadine hydrochloride, rimantadine, oseltamivir phosphate, zanamivir hydrate, or peramivir) or live vaccination within 4 weeks prior to signing of the informed consent. Has underlying chronic respiratory disease (e.g., Chronic Obstructive Pulmonary Disease (COPD), chronic bronchitis, diffuse panbronchiolitis, bronchiectasis, pulmonary emphysema, pulmonary fibrosis, bronchial asthma, or active tuberculosis). At the beginning of the study, is suspected of having bacterial respiratory infection (i.e., expectoration of purulent or mucopurulent sputum and/or infiltrate in lung in a chest x-ray, or is on antibiotics for lung disease). Has a history of gout or is under treatment for gout or hyperuricemia. Has hereditary xanthinuria. Has a history of hypouricemia (under 1 mg/dL) or xanthine calculi of the urinary tract. Has a history of hypersensitivity to an anti-viral nucleoside-analog drug targeting a viral RNA polymerase. Is using adrenocorticosteroids, except topical preparations, or immunosuppressive drugs (e.g., immunosuppressants, anticancer drugs). Has an allergy to acetaminophen or has a contraindication for acetaminophen. Has a serious chronic disease (e.g., HIV, cancer requiring chemotherapy within the preceding 6 months, moderate or severe hepatic insufficiency and/or unstable renal, cardiac, pulmonary, neurologic, vascular, or endocrinologic disease states requiring medication dose adjustments within the last 30 days). Has previously received favipiravir (T-705a). Has renal insufficiency requiring hemodialysis or central auditory processing disorder (CAPD). Has a Class II or greater cardiac impairment defined by the New York Heart Association (NYHA)Functional Classification. Has a history of alcohol or drug abuse in the preceding 2 years. Has a psychiatric disease that is not well controlled (not on a stable regimen for greater than one year) Has taken another investigational drug within 30 days prior to signing the informed consent. Is deemed by the Investigator to be ineligible for any reason. Is employed by or is related to an employee of the clinical study site. Female patients who are pregnant, breast-feeding, or have a positive urine pregnancy test at Visit 1.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo BID x 1 day, and Placebo BID x 4 days; Placebo TID x 1 day, and Placebo TID x 4 days<br>|
| Experimental: T-705 A<br>Favipiravir regimen 1: 1200 mg 3x daily (TID) on Day 1, then 600 mg TID on Days 2-5 | Drug: Favipiravir<br>* 1200 mg TID on Day 1, then 600 mg TID on Days 2-5<br>|
| Experimental: T-705 B<br>Favipiravir regimen 2: 2400 mg loading dose followed by 600 mg + 600 mg on Day 1, then 600 mg TID on Days 2-5 | Drug: Favipiravir<br>* 2400 mg loading dose followed by 600 mg + 600 mg on Day 1, then 600 mg TID on Days 2-5<br>|
| Experimental: T-705 C<br>Favipiravir regimen 3: 1800 mg BID on Day 1, then 800 mg BID for Days 2-5 | Drug: Favipiravir<br>* 1800 mg BID on Day 1, then 800mg BID for Days 2 5<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of favipiravir |  | Post-dose on Days 1 and 5: 1, 2, 4, 9, 10, and 12 hours | 
| Area Under the Curve (AUC) of favipiravir |  | Post-dose on Days 1 and 5: 1, 2, 4, 9, 10, and 12 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to alleviation of influenza symptoms |  | 15 days | 
| Adverse Event[AE] | The following information will be recorded: AE, time of onset, time of resolution (or note if ongoing), duration of event, severity, relationship to trial medication, use of concomitant medication, and/or other action taken, and action taken with study medication. | 15 days |