<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/NCT04440423</url>
  </required_header>
  <id_info>
    <org_study_id>HP8810-02</org_study_id>
    <nct_id>NCT04440423</nct_id>
  </id_info>
  <brief_title>Bioavailability of Clotiazepam 5 mg With Regards to Reference Product</brief_title>
  <official_title>Bioavailability of a Formulation of Clotiazepam 5 mg Coated Tablets With Regards to the Marketed Reference Product</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Laboratorios Andromaco S.A.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Laboratorios Andromaco S.A.</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>
      This Pivotal study will investigate the bioavailability in fasting women of 1 Tablet&#xD;
      formulations containing Clotiazepam 5 mg.&#xD;
&#xD;
      The Pivotal study will be performed at a single site with 30 subjects. Participants will take&#xD;
      1 Tablet of the test product and reference product in 2 periods and 2 sequences (either test&#xD;
      after reference or reference after test). There will be a washout of at least 7 days between&#xD;
      each study period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary objective of the study is to investigate the relative bioavailability of&#xD;
&#xD;
      Clotiazepam of 1 tablet formulation with Clotiazepam 5 mg and to demonstrate bioequivalence&#xD;
      of both formulations in terms of rate and extent of absorption:&#xD;
&#xD;
        -  Test Product: Product manufactured by Tecnandina S.A., Ecuador.&#xD;
&#xD;
        -  Reference Product: Rize [Trademark], product of Mitsubishi Tanabe Pharma, Japan.&#xD;
&#xD;
      The 90% confidence intervals for the intra-subject coefficient of variation (Test versus&#xD;
      Reference Product) for the main pharmacokinetic parameters área under the plasma&#xD;
      concentration-time curve from time zero to time t (AUC0-t) and from time zero to 72 hours&#xD;
      (AUC0-72), and maximum plasma concentration (Cmax) for total Levonorgestrel and Ethinyl&#xD;
      estradiol will be determined.&#xD;
&#xD;
      Participants will be confined in the study site for approximately 36 hours during each study&#xD;
      period (for 12 hours pre-dosing and for 12 hours post dosing) during which pharmacokinetic&#xD;
      (PK) blood samples will be obtained. 18 blood samples will be taken up to 24 hours after the&#xD;
      administration in each period. Participants will return to the site to provide additional&#xD;
      blood samples at 24 h and 34 h postdose.&#xD;
&#xD;
      The washout period between the two study periods will be at least 7 days. The samples from&#xD;
      each participant will be analyzed with 2 methods of highperformance liquid&#xD;
      chromatography-tandem mass spectrometry bioanalytical assays to quantify total Levonorgestrel&#xD;
      and Ethinyl estradiol in plasma.&#xD;
&#xD;
      The safety objective is to evaluate the tolerability of both formulations in women by&#xD;
      collecting adverse events.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 11, 2020</start_date>
  <completion_date type="Actual">March 28, 2020</completion_date>
  <primary_completion_date type="Actual">March 28, 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>Total Clotiazepam: area under the plasma concentration-time curve from 0 to 34 hours (AUC0-34).</measure>
    <time_frame>From intake and up to 34 hours after tablet intake.</time_frame>
    <description>21 samples up to 34 hours will be taken after the administration in each period.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Total Clotiazepam: area under the plasma concentration-time curve from 0 to time t (AUC0-t).</measure>
    <time_frame>From intake and up to 34 hours after tablet intake.</time_frame>
    <description>21 samples up to 34 hours will be taken after the administration in each period.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Total Clotiazepam: Maximum plasma concentration (Cmax)</measure>
    <time_frame>From intake and up to 34 hours after tablet intake.</time_frame>
    <description>21 samples up to 34 hours will be taken after the administration in each period. The Cmax will be calculated.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total Clotiazepam: Time to achieve maximum plasma concentration (tmax)</measure>
    <time_frame>From intake and up to 34 hours after tablet intake.</time_frame>
    <description>21 samples up to 34 hours will be taken after the administration in each period. The tmax will be calculated.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Bioequivalence</condition>
  <arm_group>
    <arm_group_label>Clotiazepam Test Product</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Clotiazepam Reference Product</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clotiazepam 5 mg Test Product Coated Tablets</intervention_name>
    <description>Investigational Medicinal Product</description>
    <arm_group_label>Clotiazepam Test Product</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clotiazepam 5 mg Reference Product Coated Tablets</intervention_name>
    <description>Rize (Trademark)</description>
    <arm_group_label>Clotiazepam Reference Product</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Non-pregnant and non-breastfeeding women&#xD;
&#xD;
          -  Women of childbearing age with an acceptable form of contraception during the study&#xD;
&#xD;
          -  18 to 55 years old inclusive; BMI greater than or equal to 18.51 and less than or&#xD;
             equal to 29.99&#xD;
&#xD;
          -  With results of laboratory tests, electrocardiogram and chest radiography in normal&#xD;
             and / or negative or abnormal ranges but without clinical relevance and declared&#xD;
             suitable for study by the doctor after the physical examination&#xD;
&#xD;
          -  Capable to understand the Informed Consent Form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Study Site staff or family members&#xD;
&#xD;
          -  With history of drug and/or alcohol abuse&#xD;
&#xD;
          -  Smokers more tan 3 cigarettes every 7 days&#xD;
&#xD;
          -  Vitamin supplements intake 7 days prior to the administration of the medications under&#xD;
             study&#xD;
&#xD;
          -  Any recent change in eating habits or physical exercise&#xD;
&#xD;
          -  Using of pharmacological therapy (except over the counter medication use 7 days prior&#xD;
             the study)&#xD;
&#xD;
          -  Hypersensitivity to the study drug or other related compounds, history of serious&#xD;
             adverse reactions or hypersensitivity to any medication&#xD;
&#xD;
          -  Use, during 28 days prior to the start of the study, of medications known to alter&#xD;
             liver enzyme activity&#xD;
&#xD;
          -  Consumption of beverages or food containing grapefruit or pink grapefruit, within 7&#xD;
             days prior to each administration of the study medication and consumption of alcohol,&#xD;
             caffeine or beverages or food containing xanthine 24 hours prior each administration&#xD;
             of study medication until the last sample of each period&#xD;
&#xD;
          -  History of any significant cardiovascular disease&#xD;
&#xD;
          -  Acute disease that generates significant physiological changes from the start of the&#xD;
             selection until the end of the study&#xD;
&#xD;
          -  HIV, Hepatitis B and/or C positive&#xD;
&#xD;
          -  Presence or history of thrombophlebitis, thrombosis or thromboembolic disorder, deep&#xD;
             vein thrombosis, pulmonary embolism or known coagulopathy.&#xD;
&#xD;
          -  Donation or loss of a significant volume (more tan 100 mL) of blood or plasma or&#xD;
             platelets during the 3 months prior to the start of the study&#xD;
&#xD;
          -  Subjects who have participated in any type of clinical study during the 3 months prior&#xD;
             to the start of the study&#xD;
&#xD;
          -  History of any gastrointestinal surgery that could affect drug absorption&#xD;
&#xD;
          -  Presence of fainting history or fear to blood collection&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Innolab</name>
      <address>
        <city>Santiago</city>
        <zip>7510491</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Chile</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 17, 2020</study_first_submitted>
  <study_first_submitted_qc>June 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 19, 2020</study_first_posted>
  <last_update_submitted>June 17, 2020</last_update_submitted>
  <last_update_submitted_qc>June 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- 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/NCT04440423
org study id: HP8810-02
nct id: NCT04440423
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This Pivotal study will investigate the bioavailability in fasting women of 1 Tablet
      formulations containing Clotiazepam 5 mg.

      The Pivotal study will be performed at a single site with 30 subjects. Participants will take
      1 Tablet of the test product and reference product in 2 periods and 2 sequences (either test
      after reference or reference after test). There will be a washout of at least 7 days between
      each study period.
The primary objective of the study is to investigate the relative bioavailability of

      Clotiazepam of 1 tablet formulation with Clotiazepam 5 mg and to demonstrate bioequivalence
      of both formulations in terms of rate and extent of absorption:

        -  Test Product: Product manufactured by Tecnandina S.A., Ecuador.

        -  Reference Product: Rize [Trademark], product of Mitsubishi Tanabe Pharma, Japan.

      The 90% confidence intervals for the intra-subject coefficient of variation (Test versus
      Reference Product) for the main pharmacokinetic parameters área under the plasma
      concentration-time curve from time zero to time t (AUC0-t) and from time zero to 72 hours
      (AUC0-72), and maximum plasma concentration (Cmax) for total Levonorgestrel and Ethinyl
      estradiol will be determined.

      Participants will be confined in the study site for approximately 36 hours during each study
      period (for 12 hours pre-dosing and for 12 hours post dosing) during which pharmacokinetic
      (PK) blood samples will be obtained. 18 blood samples will be taken up to 24 hours after the
      administration in each period. Participants will return to the site to provide additional
      blood samples at 24 h and 34 h postdose.

      The washout period between the two study periods will be at least 7 days. The samples from
      each participant will be analyzed with 2 methods of highperformance liquid
      chromatography-tandem mass spectrometry bioanalytical assays to quantify total Levonorgestrel
      and Ethinyl estradiol in plasma.

      The safety objective is to evaluate the tolerability of both formulations in women by
      collecting adverse events.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: None (Open Label)
measure: Total Clotiazepam: area under the plasma concentration-time curve from 0 to 34 hours (AUC0-34).
time frame: From intake and up to 34 hours after tablet intake.
description: 21 samples up to 34 hours will be taken after the administration in each period.
measure: Total Clotiazepam: area under the plasma concentration-time curve from 0 to time t (AUC0-t).
time frame: From intake and up to 34 hours after tablet intake.
description: 21 samples up to 34 hours will be taken after the administration in each period.
measure: Total Clotiazepam: Maximum plasma concentration (Cmax)
time frame: From intake and up to 34 hours after tablet intake.
description: 21 samples up to 34 hours will be taken after the administration in each period. The Cmax will be calculated.
measure: Total Clotiazepam: Time to achieve maximum plasma concentration (tmax)
time frame: From intake and up to 34 hours after tablet intake.
description: 21 samples up to 34 hours will be taken after the administration in each period. The tmax will be calculated.
arm group label: Clotiazepam Test Product
arm group type: Experimental
arm group label: Clotiazepam Reference Product
arm group type: Active Comparator
intervention type: Drug
intervention name: Clotiazepam 5 mg Test Product Coated Tablets
description: Investigational Medicinal Product
arm group label: Clotiazepam Test Product
intervention type: Drug
intervention name: Clotiazepam 5 mg Reference Product Coated Tablets
description: Rize (Trademark)
arm group label: Clotiazepam Reference Product
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Chile
responsible party type: Sponsor