A Pharmacokinetics Study of Favipiravir in Patients With Severe Influenza

Inclusion criteria

• Hospitalized males or females with a positive PCR test for influenza virus infection
• Adults aged ≥18years
• PaO2/FiO2≤300mmHg or on mechanical ventilation
• < 10 days since symptom onset
• Negative pregnancy testing for childbearing age females (under 60 years)
• Willingness to use contraception for 7 days after end of treatment
• Informed consent
• In addition, male subjects must:

• Agree not to donate sperm during the study and for 7 days following the last dose of study drug, and
• Agree to adhere strictly to one of the following contraceptive measures from the Screening Visit until 7 days after the last dose of study drug:

i. abstain from sexual intercourse or ii. have a female partner using effective means of birth control as noted below or iii. use a condom with spermicide or a second barrier method by female partner.

Female subjects

a. Of child-bearing potential must agree to adhere strictly to one of the following approved contraceptive measures during the study and for 7 days after the last dose of study drug: i. abstain from sexual intercourse or ii. have a male partner incapable of fathering a child (eg, had a vasectomy at least 6 months with history of negative semen analysis prior Screening or iii. use of one of the following methods, in combination with condom and spermicide use by a male partner: nonhormonal intrauterine device (IUD); diaphragm; or hormonal contraceptives including oral contraceptives, injectable subdermal implants, hormonal IUD, or vaginal ring b. Be unable to bear children defined as one of the following: i. absence of a menstrual period for ≥12 consecutive months with FSH confirmation, ii. be 60 years of age or greater, iii. had surgical removal of uterus or removal of both ovaries, or iv. had undergone tubal ligation >6 weeks prior to Day 1 dosing

Exclusion criteria

• Any condition that does not allow for safely following the protocol
• Patient refusal to accept invasive organ support treatment if needed
• Pregnant or breastfeeding
• Any condition resulted to reception of renal replacement therapy
• AST > 5 times upper of limit or Child Pugh score ≥ C
• Serum uric acid level > 3 times upper level of normal (430 ummol/L) associated with symptoms of gout
• 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
• Physician makes a decision that trial involvement is not in patients' best interest.
• Currently or have been involved in another anti-influenza treatment trial in the last 28 days