<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04444986</url>
  </required_header>
  <id_info>
    <org_study_id>NOV2020/01919</org_study_id>
    <nct_id>NCT04444986</nct_id>
  </id_info>
  <brief_title>Bioequivalence Study of Favir 200 mg Film Tablet Kocak Under Fasting Conditions</brief_title>
  <official_title>Open-Label, Randomised, Single Oral Dose, Two-Period, Cross-Over Trial To Assess The Bioequivalence Of Favir 200 Mg Ft In Comparison With Avigan 200 Mg Ft In Healthy Male Subjects Under Fasting Conditions</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kocak Farma</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novagenix Bioanalytical Drug R&amp;D Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Farmagen Ar-Ge Biyot. Ltd. Sti</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Kocak Farma</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A single dose of Reference product containing 200 mg favipiravir and a single dose of Test&#xD;
      product containing 200 mg favipiravir or vice versa; administered with 240 mL of water at&#xD;
      room temperature, in each period under fasting conditions with current pandemic precautions.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Favipiravir is a drug with a mechanism of action different from that of the existing&#xD;
      influenza antiviral drugs and effective against all types and sub-types of human influenza A,&#xD;
      B and C viruses in vitro, showing anti-viral activity against various influenza virus strains&#xD;
      including avian and swine viruses. Favipiravir also has shown anti-viral activity even&#xD;
      against amantadine, oseltamivir and zanamivir-resistant influenza viruses in vitro. The&#xD;
      mechanism of action of favipiravir is the selective inhibition of RNA polymerase by&#xD;
      favipiravir ribosyl triphosphate formed by cellular enzymes in the influenza virus leading to&#xD;
      antiviral activity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 5, 2020</start_date>
  <completion_date type="Actual">June 13, 2020</completion_date>
  <primary_completion_date type="Actual">June 11, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC0-tlast of favipiravir</measure>
    <time_frame>0 to 24 hours post-dose</time_frame>
    <description>AUC0-tlast of favipiravir obtained by plasma concentration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax of favipiravir</measure>
    <time_frame>0 to 24 hours post-dose</time_frame>
    <description>Cmax of favipiravir obtained by plasma concentration</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>AUC0-inf of favipiravir</measure>
    <time_frame>0 to 24 hours post-dose</time_frame>
    <description>AUC0-inf of favipiravir obtained by plasma concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax of favipiravir</measure>
    <time_frame>0 to 24 hours post-dose</time_frame>
    <description>tmax of favipiravir obtained by plasma concentration</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Bioequivalence</condition>
  <arm_group>
    <arm_group_label>FAVIR then AVIGAN</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants first received Favir 200 mg FT manufactured by Kocak in a fasting state. After a washout period of 48 hours, they then received Avigan FT200 mg manufactured by Toyama Chemical Industry Co.Ltd./ Japan in a fasting state.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AVIGAN then FAVIR</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants first received Favir 200 mg FT manufactured by Kocak in a fasting state. After a washout period of 48 hours, they then received Avigan FT200 mg manufactured by Toyama Chemical Industry Co.Ltd./ Japan in a fasting state.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FAVIR 200 MG FT</intervention_name>
    <description>FAVICOVIR containing 200 mg favipiravir manufactured by Kocak, Turkey.</description>
    <arm_group_label>AVIGAN then FAVIR</arm_group_label>
    <arm_group_label>FAVIR then AVIGAN</arm_group_label>
    <other_name>Test</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AVIGAN 200 mg FT</intervention_name>
    <description>AVIGAN containing 200 mg favipiravir manufactured by Toyama, Japan</description>
    <arm_group_label>AVIGAN then FAVIR</arm_group_label>
    <arm_group_label>FAVIR then AVIGAN</arm_group_label>
    <other_name>Reference</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy Caucasian male subjects aged between 20 and 40 years,&#xD;
&#xD;
          2. Non smokers or smoking maximum 5 cigarettes a day, those who won't smoke or drink&#xD;
             coffee during the study period,&#xD;
&#xD;
          3. Two Negative Covid-19 PCR test results.&#xD;
&#xD;
          4. Negative alcohol breath test results,&#xD;
&#xD;
          5. Normal physical examination at screening visit,&#xD;
&#xD;
          6. Having the Body Mass Index ranged between 18.5-30 kg/m2 (see Appendix I) which is in&#xD;
             the desirable range according to the age,&#xD;
&#xD;
          7. Ability to communicate adequately with the investigator himself or his&#xD;
             representatives,&#xD;
&#xD;
          8. Ability and agreement to comply with the study requirements,&#xD;
&#xD;
          9. Normal blood pressure and heart rate measured under stabilised conditions at the&#xD;
             screening visit after at least 5 minutes of rest under supine position: SBP within 100&#xD;
             to 140 mmHg, DBP within 60 to 90 mmHg and HR within 50 to 90 bpm,&#xD;
&#xD;
         10. Normal/ acceptable 12-lead electrocardiographic results at least after 5 minutes of&#xD;
             rest,&#xD;
&#xD;
         11. Laboratory results within normal range or clinically non-significant (CBC, glucose,&#xD;
             urea, uric acid, creatinine, estimated GFR (eGFR), total bilirubin, sodium, potassium,&#xD;
             calcium, chloride, SGOT (AST), SGPT (ALT), GGT, alkaline phosphatase, total protein&#xD;
             and urinalysis), drug addiction scanning in urine results in negative (amphetamine,&#xD;
             barbiturate, benzodiazepine, cannabinoid, cocaine, opiate),&#xD;
&#xD;
         12. Understanding of the study and agreement to give a written informed consent according&#xD;
             to section 20.3.&#xD;
&#xD;
         13. Understanding of that he and his partner will use a practice adequate contraception&#xD;
             during the study and at least 7 days after the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Who have atopic constitution or asthma or known allergy for favipiravir and/or any&#xD;
             other ingredients of the products.&#xD;
&#xD;
          2. Who have positive Covid-19 PCR test result.&#xD;
&#xD;
          3. Any history or presence of clinical relevance of cardiovascular, neurological,&#xD;
             musculoskeletal, haematological, hepatic, gastrointestinal, renal, pulmonary,&#xD;
             endocrinological, metabolism or psychiatric disease, any type of porphyria.&#xD;
&#xD;
          4. Symptomatic or asymptomatic orthostatic hypotension at screening or before the first&#xD;
             drug administration defined by a decrease of SBP more than 20 mmHg or DBD more than 10&#xD;
             mmHg occurs between sitting/supine to standing position subject will be excluded (if&#xD;
             it deemed necessary by the investigator),&#xD;
&#xD;
          5. Presence or history of malabsorption or any gastrointestinal surgery except&#xD;
             appendectomy or except herniotomy.&#xD;
&#xD;
          6. Subjects who have given more than 400 mL blood within the last two months before the&#xD;
             first drug administration and subjects who have participated to any drug research&#xD;
             within the last two months before the first drug administration.&#xD;
&#xD;
          7. Subjects suspected to have a high probability of non-compliance to the study procedure&#xD;
             and/or completion of the study according to the investigator's judgement.&#xD;
&#xD;
          8. Subjects who used any of prescribed systemic or topical medication (including OTC&#xD;
             medication) within 2 weeks (or six elimination half lives of this medication,&#xD;
             whichever is longer) before the initiation of the study (except single doses of&#xD;
             analgesics which have no drug interaction with study product).&#xD;
&#xD;
          9. Use of any vitamins or herbal products within 7 days prior to the initial dose of the&#xD;
             study medication.&#xD;
&#xD;
         10. History of allergic response to heparin.&#xD;
&#xD;
         11. Subjects who have any chronic disease which might interfere with absorption,&#xD;
             distribution, metabolism or excretion of the drug.&#xD;
&#xD;
         12. Subjects who regular consumed of beverages or food containing methylxanthines (e.g.&#xD;
             coffee, tea, cola, caffeine, chocolate, sodas,) equivalent to more than 500 mg&#xD;
             methylxanthines per day.&#xD;
&#xD;
         13. Subjects who has taken any grapefruit or grapefruit juice during 7 days prior to drug&#xD;
             administration, during the study.&#xD;
&#xD;
         14. History of drug abuse.&#xD;
&#xD;
         15. History of alcohol abuse and/or regular use of more than 2 units of alcohol per day or&#xD;
             10 units per week and/or positive alcohol breath test results (Note: one unit of&#xD;
             alcohol equals 250 mL beer, 125 mL wine or 25 mL spirits).&#xD;
&#xD;
         16. Positive blood test for HBV, HCV and HIV.&#xD;
&#xD;
         17. Who have relationship to the investigator.&#xD;
&#xD;
         18. Who are not suitable to any of inclusion criteria.&#xD;
&#xD;
         19. History of difficulty of swallowing.&#xD;
&#xD;
         20. Intake of depot injectable solutions (including study medications) within 6 months&#xD;
             before start of the study.&#xD;
&#xD;
         21. Intake of enzyme-inducing, organotoxic or long half-life drugs within 4 weeks before&#xD;
             start of the study.&#xD;
&#xD;
         22. Special diet due to any reason, e.g. vegetarian.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Muradiye Nacak, MD,PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Farmagen Ar-Ge Biyot. Ltd. Sti</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Taner Ezgi, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Farmagen Ar-Ge Biyot. Ltd. Sti</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Novagenix Drug R&amp;D Center</name>
      <address>
        <city>Akyurt</city>
        <state>Ankara</state>
        <zip>06970</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Farmagen Ar-Ge Biyot. Ltd. Sti.</name>
      <address>
        <city>Gaziantep</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Turkey</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>June 21, 2020</study_first_submitted>
  <study_first_submitted_qc>June 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 24, 2020</study_first_posted>
  <last_update_submitted>November 25, 2020</last_update_submitted>
  <last_update_submitted_qc>November 25, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <keyword>COVID-19 drug treatment</keyword>
  <keyword>Favipiravir</keyword>
  <keyword>Novagenix</keyword>
  <keyword>Farmagen</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Favipiravir</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol, Statistical Analysis Plan, and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 5, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/86/NCT04444986/Prot_SAP_ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04444986
org study id: NOV2020/01919
nct id: NCT04444986
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: None (Open Label)
measure: AUC0-tlast of favipiravir
time frame: 0 to 24 hours post-dose
description: AUC0-tlast of favipiravir obtained by plasma concentration
measure: Cmax of favipiravir
time frame: 0 to 24 hours post-dose
description: Cmax of favipiravir obtained by plasma concentration
measure: AUC0-inf of favipiravir
time frame: 0 to 24 hours post-dose
description: AUC0-inf of favipiravir obtained by plasma concentration
measure: tmax of favipiravir
time frame: 0 to 24 hours post-dose
description: tmax of favipiravir obtained by plasma concentration
arm group label: FAVIR then AVIGAN
arm group type: Experimental
description: Participants first received Favir 200 mg FT manufactured by Kocak in a fasting state. After a washout period of 48 hours, they then received Avigan FT200 mg manufactured by Toyama Chemical Industry Co.Ltd./ Japan in a fasting state.
arm group label: AVIGAN then FAVIR
arm group type: Experimental
description: Participants first received Favir 200 mg FT manufactured by Kocak in a fasting state. After a washout period of 48 hours, they then received Avigan FT200 mg manufactured by Toyama Chemical Industry Co.Ltd./ Japan in a fasting state.
intervention type: Drug
intervention name: FAVIR 200 MG FT
description: FAVICOVIR containing 200 mg favipiravir manufactured by Kocak, Turkey.
arm group label: AVIGAN then FAVIR
arm group label: FAVIR then AVIGAN
other name: Test
intervention type: Drug
intervention name: AVIGAN 200 mg FT
description: AVIGAN containing 200 mg favipiravir manufactured by Toyama, Japan
arm group label: AVIGAN then FAVIR
arm group label: FAVIR then AVIGAN
other name: Reference
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Muradiye Nacak, MD,PhD
role: Principal Investigator
affiliation: Farmagen Ar-Ge Biyot. Ltd. Sti
last name: Taner Ezgi, MD
role: Study Chair
affiliation: Farmagen Ar-Ge Biyot. Ltd. Sti
facility: 
facility: 
country: Turkey
responsible party type: Sponsor
mesh term: Favipiravir
sharing ipd: No
provided document: 