<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/NCT04476719</url>
  </required_header>
  <id_info>
    <org_study_id>NOV2020/01918</org_study_id>
    <nct_id>NCT04476719</nct_id>
  </id_info>
  <brief_title>The Bioequivalence Study of Umifenovir 200 mg Capsul (ATABAY, Turkey) Under Fasting Conditions</brief_title>
  <acronym>Umifenovir</acronym>
  <official_title>Open-Label, Randomised, Single Oral Dose, Two-Period, Cross-Over Trial To Assess The Bioequivalence Of Atafenovir 200 Mg Kapsul In Comparison With Arbidol 100 Mg Kapsul In Healthy Male Subjects Under Fasting Conditions</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Atabay Kimya Sanayi Ticaret A.S.</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>Atabay Kimya Sanayi Ticaret A.S.</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 umifenovir hydrochloride monohydrate&#xD;
      equivalent to 200 mg umifenovir hydrochloride and a single dose of Test product containing&#xD;
      200 mg umifenovir hydrochloride monohydrate equivalent to 200 mg umifenovir hydrochloride or&#xD;
      vice versa; administered with 240 mL of water at room temperature, in each period under&#xD;
      fasting conditions with Covid-19 Pandemic precautions.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In order to investigate the bioequivalence of all products, the 90% confidence intervals will&#xD;
      be calculated for the geometric mean ratios of test and reference for Cmax and AUC0-tlast of&#xD;
      umifenovir. These confidence intervals will then be compared with the corresponding&#xD;
      acceptance ranges.&#xD;
&#xD;
      In order to achieve a better approximation to a normal distribution, Cmax and AUC0-tlast data&#xD;
      for umifenovir will be logarithmically transformed (base e) before analysis. The sources of&#xD;
      variation will be treatments, periods, sequences and subjects within the sequence. Evaluation&#xD;
      of treatment, period, sequence and subject (nested within sequence) effects at 5% level of&#xD;
      significance will be performed. From the result, the two one-sided hypothesis at the 5% level&#xD;
      of significance will be tested by constructing the 90% confidence interval for the geometric&#xD;
      mean ratios of test/reference products. The confidence interval is calculated by&#xD;
      retransformation of the shortest confidence interval for the difference of the ln-transformed&#xD;
      mean values. Differences in tmax will be evaluated non-parametrically.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">July 9, 2020</start_date>
  <completion_date type="Anticipated">August 20, 2020</completion_date>
  <primary_completion_date type="Anticipated">July 22, 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>Primary PK Endpoint</measure>
    <time_frame>12 weeks</time_frame>
    <description>AUC0-tlast umifenovir</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Primary PK Endpoint</measure>
    <time_frame>13 weeks</time_frame>
    <description>Cmax of umifenovir</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Secondary PK Endpoint</measure>
    <time_frame>14 weeks</time_frame>
    <description>t1/2 of umifenovir</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary PK Endpoint</measure>
    <time_frame>15 weeks</time_frame>
    <description>tmax of umifenovir</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary PK Endpoint</measure>
    <time_frame>16 weeks</time_frame>
    <description>AUC0-inf of umifenovir</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Bioequivalence</condition>
  <arm_group>
    <arm_group_label>Atafenovir 200 mg Kapsül</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Capsules containing 207.009 mg umifenovir hydrochloride monohydrate equivalent to 200 mg umifenovir hydrochloride (Atabay-Turkey).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arbidol 100 mg Kapsül</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Capsules containing 103.504 umifenovir hydrochloride monohydrate equivalent to 100 mg umifenovir hydrochloride (OTC-Pharma Russia).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ATAFENOVIR 200 MG KAPSUL</intervention_name>
    <description>A 200 mg capsule 0ral administration with 240 ml water</description>
    <arm_group_label>Atafenovir 200 mg Kapsül</arm_group_label>
    <other_name>Test Drug</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ARBIDOL 100 MG KAPSUL</intervention_name>
    <description>Two 100 mg capsules will be administrated with 240 ml water orally.</description>
    <arm_group_label>Arbidol 100 mg Kapsül</arm_group_label>
    <other_name>Reference Drug</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.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Who have atopic constitution or asthma or known allergy for umifenovir 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>20 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 Director</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>Sahinbey</city>
        <state>Gaziantep</state>
        <zip>27000</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Turkey</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>July 15, 2020</study_first_submitted>
  <study_first_submitted_qc>July 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <last_update_submitted>July 15, 2020</last_update_submitted>
  <last_update_submitted_qc>July 15, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 20, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COVID-19 drug treatment</keyword>
  <keyword>Antiviral Agents</keyword>
  <keyword>Umifenovir</keyword>
  <keyword>Novagenix</keyword>
  <keyword>Farmagen</keyword>
  <keyword>Atabay</keyword>
  <!-- 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/NCT04476719
org study id: NOV2020/01918
nct id: NCT04476719
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 umifenovir hydrochloride monohydrate
      equivalent to 200 mg umifenovir hydrochloride and a single dose of Test product containing
      200 mg umifenovir hydrochloride monohydrate equivalent to 200 mg umifenovir hydrochloride or
      vice versa; administered with 240 mL of water at room temperature, in each period under
      fasting conditions with Covid-19 Pandemic precautions.
In order to investigate the bioequivalence of all products, the 90% confidence intervals will
      be calculated for the geometric mean ratios of test and reference for Cmax and AUC0-tlast of
      umifenovir. These confidence intervals will then be compared with the corresponding
      acceptance ranges.

      In order to achieve a better approximation to a normal distribution, Cmax and AUC0-tlast data
      for umifenovir will be logarithmically transformed (base e) before analysis. The sources of
      variation will be treatments, periods, sequences and subjects within the sequence. Evaluation
      of treatment, period, sequence and subject (nested within sequence) effects at 5% level of
      significance will be performed. From the result, the two one-sided hypothesis at the 5% level
      of significance will be tested by constructing the 90% confidence interval for the geometric
      mean ratios of test/reference products. The confidence interval is calculated by
      retransformation of the shortest confidence interval for the difference of the ln-transformed
      mean values. Differences in tmax will be evaluated non-parametrically.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: None (Open Label)
measure: Primary PK Endpoint
time frame: 12 weeks
description: AUC0-tlast umifenovir
measure: Primary PK Endpoint
time frame: 13 weeks
description: Cmax of umifenovir
measure: Secondary PK Endpoint
time frame: 14 weeks
description: t1/2 of umifenovir
measure: Secondary PK Endpoint
time frame: 15 weeks
description: tmax of umifenovir
measure: Secondary PK Endpoint
time frame: 16 weeks
description: AUC0-inf of umifenovir
arm group label: Atafenovir 200 mg Kapsül
arm group type: Experimental
description: Capsules containing 207.009 mg umifenovir hydrochloride monohydrate equivalent to 200 mg umifenovir hydrochloride (Atabay-Turkey).
arm group label: Arbidol 100 mg Kapsül
arm group type: Active Comparator
description: Capsules containing 103.504 umifenovir hydrochloride monohydrate equivalent to 100 mg umifenovir hydrochloride (OTC-Pharma Russia).
intervention type: Drug
intervention name: ATAFENOVIR 200 MG KAPSUL
description: A 200 mg capsule 0ral administration with 240 ml water
arm group label: Atafenovir 200 mg Kapsül
other name: Test Drug
intervention type: Drug
intervention name: ARBIDOL 100 MG KAPSUL
description: Two 100 mg capsules will be administrated with 240 ml water orally.
arm group label: Arbidol 100 mg Kapsül
other name: Reference Drug
criteria: 
gender: Male
minimum age: 20 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 Director
affiliation: Farmagen Ar-Ge Biyot. Ltd. Sti
facility: 
facility: 
country: Turkey
responsible party type: Sponsor