Bioequivalence Study of Favipiravir 200 mg Film Tablet (Novelfarma, Turkey) Under Fasting Conditions
Bioequivalence Study of Favipiravir 200 mg Film Tablet (Novelfarma, Turkey) Under Fasting Conditions
A single dose of Reference product containing 200 mg favipiravir and a single dose of Test
 product containing 200 mg favipiravir or vice versa; administered with 240 mL of water at
 room temperature, in each period under fasting conditions with current pandemic precautions.
Favipiravir is a drug with a mechanism of action different from that of the existing
 influenza antiviral drugs and effective against all types and sub-types of human influenza A,
 B and C viruses in vitro, showing anti-viral activity against various influenza virus strains
 including avian and swine viruses. Favipiravir also has shown anti-viral activity even
 against amantadine, oseltamivir and zanamivir-resistant influenza viruses in vitro. The
 mechanism of action of favipiravir is the selective inhibition of RNA polymerase by
 favipiravir ribosyl triphosphate formed by cellular enzymes in the influenza virus leading to
 antiviral activity.
Inclusion Criteria:

 1. Healthy Caucasian male subjects aged between 20 and 40 years,

 2. Non smokers or smoking maximum 5 cigarettes a day, those who won't smoke or drink
 coffee during the study period,

 3. Two Negative Covid-19 PCR test results.

 4. Negative alcohol breath test results,

 5. Normal physical examination at screening visit,

 6. Having the Body Mass Index ranged between 18.5-30 kg/m2 (see Appendix I) which is in
 the desirable range according to the age,

 7. Ability to communicate adequately with the investigator himself or his
 representatives,

 8. Ability and agreement to comply with the study requirements,

 9. Normal blood pressure and heart rate measured under stabilised conditions at the
 screening visit after at least 5 minutes of rest under supine position: SBP within 100
 to 140 mmHg, DBP within 60 to 90 mmHg and HR within 50 to 90 bpm,

 10. Normal/ acceptable 12-lead electrocardiographic results at least after 5 minutes of
 rest,

 11. Laboratory results within normal range or clinically non-significant (CBC, glucose,
 urea, uric acid, creatinine, estimated GFR (eGFR), total bilirubin, sodium, potassium,
 calcium, chloride, SGOT (AST), SGPT (ALT), GGT, alkaline phosphatase, total protein
 and urinalysis), drug addiction scanning in urine results in negative (amphetamine,
 barbiturate, benzodiazepine, cannabinoid, cocaine, opiate),

 12. Understanding of the study and agreement to give a written informed consent according
 to section 20.3.

 13. Understanding of that he and his partner will use a practice adequate contraception
 during the study and at least 7 days after the study.

 14. Volunteer's compliance with isolation rules defined at study protocol.

 Exclusion Criteria:

 1. Who have atopic constitution or asthma or known allergy for favipiravir and/or any
 other ingredients of the products.

 2. Who have positive Covid-19 PCR test result.

 3. Any history or presence of clinical relevance of cardiovascular, neurological,
 musculoskeletal, haematological, hepatic, gastrointestinal, renal, pulmonary,
 endocrinological, metabolism or psychiatric disease, any type of porphyria.

 4. Symptomatic or asymptomatic orthostatic hypotension at screening or before the first
 drug administration defined by a decrease of SBP more than 20 mmHg or DBD more than 10
 mmHg occurs between sitting/supine to standing position subject will be excluded (if
 it deemed necessary by the investigator),

 5. Presence or history of malabsorption or any gastrointestinal surgery except
 appendectomy or except herniotomy.

 6. Subjects who have given more than 400 mL blood within the last two months before the
 first drug administration and subjects who have participated to any drug research
 within the last two months before the first drug administration.

 7. Subjects suspected to have a high probability of non-compliance to the study procedure
 and/or completion of the study according to the investigator's judgement.

 8. Subjects who used any of prescribed systemic or topical medication (including OTC
 medication) within 2 weeks (or six elimination half lives of this medication,
 whichever is longer) before the initiation of the study (except single doses of
 analgesics which have no drug interaction with study product).

 9. Use of any vitamins or herbal products within 7 days prior to the initial dose of the
 study medication.

 10. History of allergic response to heparin.

 11. Subjects who have any chronic disease which might interfere with absorption,
 distribution, metabolism or excretion of the drug.

 12. Subjects who regular consumed of beverages or food containing methylxanthines (e.g.
 coffee, tea, cola, caffeine, chocolate, sodas,) equivalent to more than 500 mg
 methylxanthines per day.

 13. Subjects who has taken any grapefruit or grapefruit juice during 7 days prior to drug
 administration, during the study.

 14. History of drug abuse.

 15. History of alcohol abuse and/or regular use of more than 2 units of alcohol per day or
 10 units per week and/or positive alcohol breath test results (Note: one unit of
 alcohol equals 250 mL beer, 125 mL wine or 25 mL spirits).

 16. Positive blood test for HBV, HCV and HIV.

 17. Who have relationship to the investigator.

 18. Who are not suitable to any of inclusion criteria.

 19. History of difficulty of swallowing.

 20. Intake of depot injectable solutions (including study medications) within 6 months
 before start of the study.

 21. Intake of enzyme-inducing, organotoxic or long half-life drugs within 4 weeks before
 start of the study.

 22. Special diet due to any reason, e.g. vegetarian.