<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/NCT01682577</url>
  </required_header>
  <id_info>
    <org_study_id>PR.122/EQL/2008</org_study_id>
    <nct_id>NCT01682577</nct_id>
  </id_info>
  <brief_title>Bioequivalence Study of Two Formulations of Perindopril 4 mg Tablet Under Fasting Condition</brief_title>
  <official_title>Bioequivalence Study of 4 mg Perindopril Tablets Produced by PT Dexa Medica in Comparison With the Reference Tablets (Prexum® 4 mg, Servier)Under Fasting Condition</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dexa Medica Group</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Dexa Medica Group</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this study was to find out whether the bioavailability of PT Dexa Medica's&#xD;
      formulation of 4 mg perindopril tert-butylamine tablets was equivalent to that of the&#xD;
      innovator's product (Prexum® 4 mg, Servier).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The participating subjects were required to have an overnight fast and in the next morning&#xD;
      were given orally one tablet of the test drug (Perindopril 4 mg tablets of PT Dexa Medica) or&#xD;
      one tablet of the reference drug (Prexum® 4 mg, Servier).&#xD;
&#xD;
      Blood samples were drawn immediately before taking the drug (control), and at 20, 40 minutes,&#xD;
      and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 192 hours after drug administration.&#xD;
&#xD;
      Three weeks after the first drug administration (washout period), the procedure was repeated&#xD;
      using the alternate drug.&#xD;
&#xD;
      The pharmacokinetic parameters, including AUCt, AUCinf, Cmax, t max, and t1/2, were&#xD;
      determined based on the concentrations of the perindopril parent compound and the metabolite&#xD;
      perindoprilat, using high-performance liquid chromatography method with tandem mass&#xD;
      spectrometry detector (LC-MS/MS).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2008</start_date>
  <completion_date type="Actual">December 2008</completion_date>
  <primary_completion_date type="Actual">November 2008</primary_completion_date>
  <phase>N/A</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>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under concentration-time curve (AUC)of perindopril parent compound</measure>
    <time_frame>192 hours</time_frame>
    <description>Relative bioavailability (primarily measured by AUCt and AUCinf) between two perindopril 4 mg tablet formulations (test and reference formulations) under fasting condition. The AUC was measured based on the plasma concentration of perindopril parent compound.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under concentration-time curve (AUC)of perindoprilat</measure>
    <time_frame>192 hours</time_frame>
    <description>Relative bioavailability (primarily measured by AUCt and AUCinf) between two perindopril 4 mg tablet formulations (test and reference formulations) under fasting condition. The AUC was measured based on the plasma concentration of the active metabolite, perindoprilat.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Peak plasma concentration (Cmax)of perindopril parent compound</measure>
    <time_frame>192 hours</time_frame>
    <description>Relative bioavailability (secondarily measured by Cmax) between two perindopril 4 mg tablet formulations (test and reference formulations) under fasting condition. The Cmax was measured based on the plasma concentration of perindopril parent compound.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak plasma concentration (Cmax)of perindoprilat</measure>
    <time_frame>192 hours</time_frame>
    <description>Relative bioavailability (secondarily measured by Cmax) between two perindopril 4 mg tablet formulations (test and reference formulations) under fasting condition. The Cmax was measured based on the plasma concentration of the active metabolite, perindoprilat.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to achieve the peak plasma concentration (tmax)of perindopril parent compound</measure>
    <time_frame>192 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to achieve the peak plasma concentration (tmax)of perindoprilat</measure>
    <time_frame>192 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Elimination half-life (t1/2)of perindopril parent compound</measure>
    <time_frame>192 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Elimination half-life (t1/2)of perindoprilat</measure>
    <time_frame>192 hours</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Perindopril 4 mg tablets of PT Dexa Medica</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group I (Test product): each tablet contains perindopril tert-butylamine salt 4 mg.&#xD;
A single dose of perindopril tablet of PT Dexa Medica was given to each of study subjects.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Perindopril 4 mg tablets of Servier</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Group II (Reference product) : each tablet contains perindopril tert-butylamine salt 4 mg.&#xD;
A single dose of perindopril (Prexum) tablets of Servier was given to each of study subjects.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Perindopril 4 mg tablets of PT Dexa Medica</intervention_name>
    <description>Test product was given as a single dose, under the procedure as described in the Section: Detailed description of the study.</description>
    <arm_group_label>Perindopril 4 mg tablets of PT Dexa Medica</arm_group_label>
    <other_name>Test Product: Perindopril 4 mg tablets of PT Dexa Medica.</other_name>
    <other_name>Each tablet contains perindopril tert-butylamine salt 4 mg</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Perindopril 4 mg tablets of Servier</intervention_name>
    <description>Reference product was given as a single dose, under the procedure as described in the Section: Detailed description of the study.</description>
    <arm_group_label>Perindopril 4 mg tablets of Servier</arm_group_label>
    <other_name>Reference product: Prexum® 4 mg, produced by Servier.</other_name>
    <other_name>Each tablet contains Perindopril tert-butylamine salt 4 mg.</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male and female subjects&#xD;
&#xD;
          -  Aged 18-55 years inclusive&#xD;
&#xD;
          -  A body mass index in the range of 18-25 kg/m2&#xD;
&#xD;
          -  Able to participate, communicate well with the investigators and willing to give&#xD;
             informed consent&#xD;
&#xD;
          -  Non-smokers&#xD;
&#xD;
          -  Vital signs (after 10 minutes resting) are within the following ranges:&#xD;
&#xD;
               -  systolic blood pressure 100-125 mmHg&#xD;
&#xD;
               -  diastolic blood pressure 60-80 mmHg&#xD;
&#xD;
               -  pulse rate 60-90 bpm&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Known hypersensitivity or contraindication to perindopril&#xD;
&#xD;
          -  Intake of any prescription drug within 14 days of this study's first dosing day&#xD;
&#xD;
          -  Intake of any non-prescription drug, food supplement, or herbal medicine within 7 days&#xD;
             of this study's first dosing day&#xD;
&#xD;
          -  History or presence of any liver dysfunction (ALT, alkaline phosphatase, total&#xD;
             bilirubin ≥ 1.5 ULN)&#xD;
&#xD;
          -  History of any bleeding or coagulation disorders&#xD;
&#xD;
          -  Clinically significant ECG abnormalities&#xD;
&#xD;
          -  Clinically significant haematology abnormalities&#xD;
&#xD;
          -  Renal insufficiency (plasma creatinine concentration ≥ 1.4 mg/dL)&#xD;
&#xD;
          -  Any surgical or medical condition which might significantly alter the absorption,&#xD;
             distribution, metabolism, or excretion of the study drug&#xD;
&#xD;
          -  A donation or loss of 500 mL (or more) of blood within 3 months before this study's&#xD;
             first dosing day&#xD;
&#xD;
          -  A positive hepatitis B surface antigen (HBsAg), anti-HCV, and anti-HIV&#xD;
&#xD;
          -  History of drug or alcohol abuse within 12 months prior to screening of this study&#xD;
&#xD;
          -  Participation in a previous study within 3 months of this study's first dosing day&#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>Danang A Yunaidi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>PT Equilab International</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>PT Equilab International</name>
      <address>
        <city>Jakarta</city>
        <zip>12430</zip>
        <country>Indonesia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Indonesia</country>
  </location_countries>
  <reference>
    <citation>Bellissant E, Giudicelli JF. Pharmacokinetic-pharmacodynamic model for perindoprilat regional haemodynamic effects in healthy volunteers and in congestive heart failure patients. Br J Clin Pharmacol. 2001 Jul;52(1):25-33. doi: 10.1046/j.0306-5251.2001.01410.x.</citation>
    <PMID>11453887</PMID>
  </reference>
  <reference>
    <citation>Louis WJ, Workman BS, Conway EL, Worland P, Rowley K, Drummer O, McNeil JJ, Harris G, Jarrott B. Single-dose and steady-state pharmacokinetics and pharmacodynamics of perindopril in hypertensive subjects. J Cardiovasc Pharmacol. 1992 Sep;20(3):505-11. doi: 10.1097/00005344-199209000-00024.</citation>
    <PMID>1279299</PMID>
  </reference>
  <reference>
    <citation>Sennesael J, Ali A, Sweny P, Vandenburg M, Slovic D, Dratwa M, Resplandy G, Genissel P, Desche P. The pharmacokinetics of perindopril and its effects on serum angiotensin converting enzyme activity in hypertensive patients with chronic renal failure. Br J Clin Pharmacol. 1992 Jan;33(1):93-9. doi: 10.1111/j.1365-2125.1992.tb04006.x.</citation>
    <PMID>1311597</PMID>
  </reference>
  <verification_date>September 2012</verification_date>
  <study_first_submitted>September 3, 2012</study_first_submitted>
  <study_first_submitted_qc>September 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2012</study_first_posted>
  <last_update_submitted>September 6, 2012</last_update_submitted>
  <last_update_submitted_qc>September 6, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 11, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Perindopril</keyword>
  <keyword>Perindoprilat</keyword>
  <keyword>Bioequivalence</keyword>
  <keyword>Pharmacokinetic</keyword>
  <keyword>Angiotensin-converting enzyme inhibitor</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Perindopril</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/NCT01682577
org study id: PR.122/EQL/2008
nct id: NCT01682577
lead sponsor: 
has dmc: No
The objective of this study was to find out whether the bioavailability of PT Dexa Medica's
      formulation of 4 mg perindopril tert-butylamine tablets was equivalent to that of the
      innovator's product (Prexum® 4 mg, Servier).
The participating subjects were required to have an overnight fast and in the next morning
      were given orally one tablet of the test drug (Perindopril 4 mg tablets of PT Dexa Medica) or
      one tablet of the reference drug (Prexum® 4 mg, Servier).

      Blood samples were drawn immediately before taking the drug (control), and at 20, 40 minutes,
      and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, 192 hours after drug administration.

      Three weeks after the first drug administration (washout period), the procedure was repeated
      using the alternate drug.

      The pharmacokinetic parameters, including AUCt, AUCinf, Cmax, t max, and t1/2, were
      determined based on the concentrations of the perindopril parent compound and the metabolite
      perindoprilat, using high-performance liquid chromatography method with tandem mass
      spectrometry detector (LC-MS/MS).
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Single (Investigator)
measure: Area under concentration-time curve (AUC)of perindopril parent compound
time frame: 192 hours
description: Relative bioavailability (primarily measured by AUCt and AUCinf) between two perindopril 4 mg tablet formulations (test and reference formulations) under fasting condition. The AUC was measured based on the plasma concentration of perindopril parent compound.
measure: Area under concentration-time curve (AUC)of perindoprilat
time frame: 192 hours
description: Relative bioavailability (primarily measured by AUCt and AUCinf) between two perindopril 4 mg tablet formulations (test and reference formulations) under fasting condition. The AUC was measured based on the plasma concentration of the active metabolite, perindoprilat.
measure: Peak plasma concentration (Cmax)of perindopril parent compound
time frame: 192 hours
description: Relative bioavailability (secondarily measured by Cmax) between two perindopril 4 mg tablet formulations (test and reference formulations) under fasting condition. The Cmax was measured based on the plasma concentration of perindopril parent compound.
measure: Peak plasma concentration (Cmax)of perindoprilat
time frame: 192 hours
description: Relative bioavailability (secondarily measured by Cmax) between two perindopril 4 mg tablet formulations (test and reference formulations) under fasting condition. The Cmax was measured based on the plasma concentration of the active metabolite, perindoprilat.
measure: Time to achieve the peak plasma concentration (tmax)of perindopril parent compound
time frame: 192 hours
measure: Time to achieve the peak plasma concentration (tmax)of perindoprilat
time frame: 192 hours
measure: Elimination half-life (t1/2)of perindopril parent compound
time frame: 192 hours
measure: Elimination half-life (t1/2)of perindoprilat
time frame: 192 hours
arm group label: Perindopril 4 mg tablets of PT Dexa Medica
arm group type: Experimental
description: Group I (Test product): each tablet contains perindopril tert-butylamine salt 4 mg.
A single dose of perindopril tablet of PT Dexa Medica was given to each of study subjects.
arm group label: Perindopril 4 mg tablets of Servier
arm group type: Active Comparator
description: Group II (Reference product) : each tablet contains perindopril tert-butylamine salt 4 mg.
A single dose of perindopril (Prexum) tablets of Servier was given to each of study subjects.
intervention type: Drug
intervention name: Perindopril 4 mg tablets of PT Dexa Medica
description: Test product was given as a single dose, under the procedure as described in the Section: Detailed description of the study.
arm group label: Perindopril 4 mg tablets of PT Dexa Medica
other name: Test Product: Perindopril 4 mg tablets of PT Dexa Medica.
other name: Each tablet contains perindopril tert-butylamine salt 4 mg
intervention type: Drug
intervention name: Perindopril 4 mg tablets of Servier
description: Reference product was given as a single dose, under the procedure as described in the Section: Detailed description of the study.
arm group label: Perindopril 4 mg tablets of Servier
other name: Reference product: Prexum® 4 mg, produced by Servier.
other name: Each tablet contains Perindopril tert-butylamine salt 4 mg.
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Danang A Yunaidi, MD
role: Principal Investigator
affiliation: PT Equilab International
facility: 
country: Indonesia
citation: Bellissant E, Giudicelli JF. Pharmacokinetic-pharmacodynamic model for perindoprilat regional haemodynamic effects in healthy volunteers and in congestive heart failure patients. Br J Clin Pharmacol. 2001 Jul;52(1):25-33. doi: 10.1046/j.0306-5251.2001.01410.x.
PMID: 11453887
citation: Louis WJ, Workman BS, Conway EL, Worland P, Rowley K, Drummer O, McNeil JJ, Harris G, Jarrott B. Single-dose and steady-state pharmacokinetics and pharmacodynamics of perindopril in hypertensive subjects. J Cardiovasc Pharmacol. 1992 Sep;20(3):505-11. doi: 10.1097/00005344-199209000-00024.
PMID: 1279299
citation: Sennesael J, Ali A, Sweny P, Vandenburg M, Slovic D, Dratwa M, Resplandy G, Genissel P, Desche P. The pharmacokinetics of perindopril and its effects on serum angiotensin converting enzyme activity in hypertensive patients with chronic renal failure. Br J Clin Pharmacol. 1992 Jan;33(1):93-9. doi: 10.1111/j.1365-2125.1992.tb04006.x.
PMID: 1311597
responsible party type: Sponsor
mesh term: Perindopril