<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/NCT02252692</url>
  </required_header>
  <id_info>
    <org_study_id>2014-000956-28</org_study_id>
    <nct_id>NCT02252692</nct_id>
  </id_info>
  <brief_title>Relative Bioavailability Study With Enalapril in Healthy Volunteers</brief_title>
  <official_title>Relative Bioavailability of Enalapril Administered as Orodispersible Minitablets in Healthy Adults</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ethicare GmbH</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>European Commission</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Ethicare GmbH</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Phase I study in healthy adult male and female volunteers to compare the bioavailability of&#xD;
      enalapril administered in orodispersible Minitablets with or without water in comparison to&#xD;
      the standard galenic tablet formulation of enalapril. The standard pharmacokinetic parameters&#xD;
      will be calculated from the bioanalytical results for enalapril and enalaprilat and compared&#xD;
      in a descriptive statistical analysis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Trial design: Open label, randomized, 3-way cross-over, 3-treatments, 3-periods in 24 healthy&#xD;
      male and female adult subjects.&#xD;
&#xD;
      Primary objectives:&#xD;
&#xD;
        1. To assess the relative bioavailability of 10 mg enalapril administered as orodispersible&#xD;
           minitablets (ODMT) with water versus a standard enalapril tablet formulation (reference&#xD;
           product: Renitec® 2 x 5 mg tablets) taken with water;&#xD;
&#xD;
        2. To assess the relative bioavailability of 10 mg enalapril administered as orodispersible&#xD;
           minitablets (ODMT) dispersed in the oral cavity versus a standard enalapril tablet&#xD;
           formulation (reference product: Renitec® 2 x 5 mg tablets) taken with water.&#xD;
&#xD;
      Secondary objectives:&#xD;
&#xD;
        1. To assess whether the PK of enalapril is affected when the orodispersible minitablet&#xD;
           (ODMT) is entirely swallowed with water versus dispersion in the oral cavity.&#xD;
&#xD;
        2. To assess the general safety and tolerability including local tolerability and&#xD;
           palatability of enalapril administered as orodispersible minitablet (ODMT).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>August 2014</start_date>
  <completion_date type="Anticipated">October 2014</completion_date>
  <primary_completion_date type="Anticipated">October 2014</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC 0-∞</measure>
    <time_frame>predose, 10 min, 20 min, 30 min, 45 min, 1 hour, 1.25 hours,1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose</time_frame>
    <description>Area under the serum concentration-time curve from time of administration to infinite time for enalaprilat</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety parameters</measure>
    <time_frame>0-48 hours post dose, at follow-up visit</time_frame>
    <description>adverse events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tolerability Outcome Parameter</measure>
    <time_frame>Immediately and 10 minutes after orodispersible minitablet administration</time_frame>
    <description>orodispersible minitablet palatability questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC 0-∞</measure>
    <time_frame>predose, 10 min, 20 min, 30 min, 45 min, 1 hour, 1.25 hours,1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose</time_frame>
    <description>Area under the serum-concentration time curve from time of administration extrapolated to infinite time for enalapil</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC 0-t</measure>
    <time_frame>predose, 10 min, 20 min, 30 min, 45 min, 1 hour, 1.25 hours,1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose</time_frame>
    <description>Area under the serum concentration-time curve from from administration to the last measurable concentration or last sampling time point (48h) for enalapril</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC 0-t</measure>
    <time_frame>predose, 10 min, 20 min, 30 min, 45 min, 1 hour, 1.25 hours,1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose</time_frame>
    <description>Area under the serum concentration-time curve from from administration to the last measurable concentration or last sampling time point (48h) for enalaprilat</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax</measure>
    <time_frame>predose, 10 min, 20 min, 30 min, 45 min, 1 hour, 1.25 hours,1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose</time_frame>
    <description>Maximum serum concentration for enalapril</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax</measure>
    <time_frame>predose, 10 min, 20 min, 30 min, 45 min, 1 hour, 1.25 hours,1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose</time_frame>
    <description>Maximum serum concentration of enalaprilat</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax</measure>
    <time_frame>predose, 10 min, 20 min, 30 min, 45 min, 1 hour, 1.25 hours,1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose</time_frame>
    <description>Time of maximum serum concentration of enalapril</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax</measure>
    <time_frame>predose, 10 min, 20 min, 30 min, 45 min, 1 hour, 1.25 hours,1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose</time_frame>
    <description>Time of maximum serum concentration for enalaprilat</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ae</measure>
    <time_frame>0-2, 2-4, 4-8, 8-12, 12-24, 24-36, 36-48 hours post-dose</time_frame>
    <description>Amount of enalaprilat or the sum of enalapril and enalaprilat excreted in urine over the time interval 0-t</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">24</enrollment>
  <condition>Heart Failure</condition>
  <arm_group>
    <arm_group_label>Enalapril</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Renitec® 2 x 5 mg tablets administered at once, to be entirely swallowed with 240 ml water</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Enalapril ODMT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 x 1mg of Enalapril ODMT, swallowed entirely with 240ml of water</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Enalapril ODMT dispersed</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 x 1mg of Enalapril ODMT, dispersed on tongue</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enalapril</intervention_name>
    <description>oral administration</description>
    <arm_group_label>Enalapril</arm_group_label>
    <arm_group_label>Enalapril ODMT</arm_group_label>
    <arm_group_label>Enalapril ODMT dispersed</arm_group_label>
    <other_name>Renitec</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy male and female subjects aged between 18 and 55 years, inclusive.&#xD;
&#xD;
          2. Body mass index (BMI) between 18.5 and 30 kg/m2 inclusive (BMI = weight/height2).&#xD;
&#xD;
          3. Non-smoker (not smoked for at least 3 months prior to screening).&#xD;
&#xD;
          4. Physical examinations, clinical laboratory values, vital signs and ECGs are clinically&#xD;
             acceptable to the investigator.&#xD;
&#xD;
          5. Subjects must have signed an informed consent document indicating that they understand&#xD;
             the purpose of, and procedures required for the study and are willing to participate&#xD;
             in the study and comply with the study procedures and restrictions.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History or evidence of clinically significant disorder (including psychiatric),&#xD;
             condition or disease that, in the opinion of the investigator would pose a risk to&#xD;
             subject safety or interfere with the study evaluation, procedures, or completion.&#xD;
&#xD;
          2. Women who are lactating/breastfeeding.&#xD;
&#xD;
          3. Women planning to become pregnant during the duration of the study.&#xD;
&#xD;
          4. Men with pregnant partners or whose partners plan to become pregnant during the study.&#xD;
&#xD;
          5. Positive pregnancy test (women) on screening or predose.&#xD;
&#xD;
          6. A baseline systolic BP ≥ 140 or &lt; 90 mmHg and/or a baseline diastolic BP of ≥ 90 or&#xD;
             &lt;50 mmHg. A baseline ECG QTcB &gt; 440 ms (males) or &gt;450 ms (females) or heart rate &gt;100&#xD;
             bpm.&#xD;
&#xD;
          7. Positive for human immunodeficiency virus (HIV) antibodies, hepatitis B surface&#xD;
             antigen, or hepatitis C antibodies at screening.&#xD;
&#xD;
          8. Known substance abuse (eg, alcohol, illicit or illegal drugs) within 1 year of dosing.&#xD;
&#xD;
          9. Positive test for drug or alcohol use at screening. If the retest during the screening&#xD;
             period is negative, subject can be included.&#xD;
&#xD;
         10. Inability or unwillingness to refrain from alcohol consumption 24 hours prior to study&#xD;
             visits and to limit consumption throughout the course of the study.&#xD;
&#xD;
         11. Has had major surgery, donated or lost 500 mL or more of blood within 2 months of the&#xD;
             first study treatment or has a history of chronic anemia.&#xD;
&#xD;
         12. Receiving or has received any investigational drug (or is currently using an&#xD;
             investigational drug or device) within 30 days or 5 half-lives (whichever is longer),&#xD;
             prior to receiving the first study treatment.&#xD;
&#xD;
         13. Use of any over-the-counter or prescription medications within 7 days or 5 half-lives&#xD;
             (whichever is longer), prior to receiving the first study treatment. However, if a&#xD;
             subject has to use medication within 7 days of the first study drug administration,&#xD;
             he/she can be included in the study the study if according to the investigator the&#xD;
             medication is not relevant within the context of the trial. Paracetamol (up to 2 g per&#xD;
             day) for analgesia, and hormonal birth control medication will be allowed.&#xD;
&#xD;
         14. Use of any herbal medicines (eg. St. John's wort), vitamins, and supplements consumed&#xD;
             by the subject within 7 days prior to receiving the first study treatment. However, if&#xD;
             a subject has used herbal medicines (eg, St. John's wort), vitamins, and supplements&#xD;
             medication within 7 days of the first study drug administration, he/she can be&#xD;
             included in the study if according to the investigator the medication is not relevant&#xD;
             within the context of the trial.&#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>
  <overall_official>
    <last_name>Jan De Hoon, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Center of Clinical Pharmacology, University Hospital Leuven, Leuven, Belgium</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Center for Clinical Pharmacology, UZ Leuven</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 6, 2014</study_first_submitted>
  <study_first_submitted_qc>September 26, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 30, 2014</study_first_posted>
  <last_update_submitted>September 26, 2014</last_update_submitted>
  <last_update_submitted_qc>September 26, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 30, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Bioavailability</keyword>
  <keyword>pharmacokinetics</keyword>
  <keyword>enalapril</keyword>
  <keyword>enalaprilat</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Enalapril</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02252692
org study id: 2014-000956-28
nct id: NCT02252692
lead sponsor: 
collaborator: 
has dmc: No
Phase I study in healthy adult male and female volunteers to compare the bioavailability of
      enalapril administered in orodispersible Minitablets with or without water in comparison to
      the standard galenic tablet formulation of enalapril. The standard pharmacokinetic parameters
      will be calculated from the bioanalytical results for enalapril and enalaprilat and compared
      in a descriptive statistical analysis.
Trial design: Open label, randomized, 3-way cross-over, 3-treatments, 3-periods in 24 healthy
      male and female adult subjects.

      Primary objectives:

        1. To assess the relative bioavailability of 10 mg enalapril administered as orodispersible
           minitablets (ODMT) with water versus a standard enalapril tablet formulation (reference
           product: Renitec® 2 x 5 mg tablets) taken with water;

        2. To assess the relative bioavailability of 10 mg enalapril administered as orodispersible
           minitablets (ODMT) dispersed in the oral cavity versus a standard enalapril tablet
           formulation (reference product: Renitec® 2 x 5 mg tablets) taken with water.

      Secondary objectives:

        1. To assess whether the PK of enalapril is affected when the orodispersible minitablet
           (ODMT) is entirely swallowed with water versus dispersion in the oral cavity.

        2. To assess the general safety and tolerability including local tolerability and
           palatability of enalapril administered as orodispersible minitablet (ODMT).
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: AUC 0-∞
time frame: predose, 10 min, 20 min, 30 min, 45 min, 1 hour, 1.25 hours,1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
description: Area under the serum concentration-time curve from time of administration to infinite time for enalaprilat
measure: Safety parameters
time frame: 0-48 hours post dose, at follow-up visit
description: adverse events
measure: Tolerability Outcome Parameter
time frame: Immediately and 10 minutes after orodispersible minitablet administration
description: orodispersible minitablet palatability questionnaire
measure: AUC 0-∞
time frame: predose, 10 min, 20 min, 30 min, 45 min, 1 hour, 1.25 hours,1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
description: Area under the serum-concentration time curve from time of administration extrapolated to infinite time for enalapil
measure: AUC 0-t
time frame: predose, 10 min, 20 min, 30 min, 45 min, 1 hour, 1.25 hours,1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
description: Area under the serum concentration-time curve from from administration to the last measurable concentration or last sampling time point (48h) for enalapril
measure: AUC 0-t
time frame: predose, 10 min, 20 min, 30 min, 45 min, 1 hour, 1.25 hours,1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
description: Area under the serum concentration-time curve from from administration to the last measurable concentration or last sampling time point (48h) for enalaprilat
measure: Cmax
time frame: predose, 10 min, 20 min, 30 min, 45 min, 1 hour, 1.25 hours,1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
description: Maximum serum concentration for enalapril
measure: Cmax
time frame: predose, 10 min, 20 min, 30 min, 45 min, 1 hour, 1.25 hours,1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
description: Maximum serum concentration of enalaprilat
measure: tmax
time frame: predose, 10 min, 20 min, 30 min, 45 min, 1 hour, 1.25 hours,1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
description: Time of maximum serum concentration of enalapril
measure: tmax
time frame: predose, 10 min, 20 min, 30 min, 45 min, 1 hour, 1.25 hours,1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 hours post-dose
description: Time of maximum serum concentration for enalaprilat
measure: Ae
time frame: 0-2, 2-4, 4-8, 8-12, 12-24, 24-36, 36-48 hours post-dose
description: Amount of enalaprilat or the sum of enalapril and enalaprilat excreted in urine over the time interval 0-t
arm group label: Enalapril
arm group type: Active Comparator
description: Renitec® 2 x 5 mg tablets administered at once, to be entirely swallowed with 240 ml water
arm group label: Enalapril ODMT
arm group type: Experimental
description: 10 x 1mg of Enalapril ODMT, swallowed entirely with 240ml of water
arm group label: Enalapril ODMT dispersed
arm group type: Experimental
description: 10 x 1mg of Enalapril ODMT, dispersed on tongue
intervention type: Drug
intervention name: Enalapril
description: oral administration
arm group label: Enalapril
arm group label: Enalapril ODMT
arm group label: Enalapril ODMT dispersed
other name: Renitec
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jan De Hoon, Professor
role: Principal Investigator
affiliation: Center of Clinical Pharmacology, University Hospital Leuven, Leuven, Belgium
facility: 
country: Belgium
responsible party type: Sponsor
mesh term: Heart Failure
mesh term: Enalapril