<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/NCT02215005</url>
  </required_header>
  <id_info>
    <org_study_id>1236.6</org_study_id>
    <nct_id>NCT02215005</nct_id>
  </id_info>
  <brief_title>Steady State Pharmacokinetics of Telmisartan, Ramipril or the Combination Following Repeated Oral Doses to Healthy Male and Female Volunteers</brief_title>
  <official_title>Steady State Pharmacokinetics of 80 mg Telmisartan (Micardis®), 10 mg Ramipril (Delix®) or the Combination Following Repeated Oral Doses to Healthy Male and Female Volunteers (an Open-label, Randomised, Multiple-dose, Three-way Crossover Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      The main objective was to investigate the effect of concurrent dosing of 10 mg ramipril and&#xD;
      80 mg telmisartan on the multiple-dose pharmacokinetics of telmisartan and ramipril.&#xD;
      Therefore the relative bioavailability of telmisartan and ramipril given in combination was&#xD;
      determined in comparison with either telmisartan or ramipril given alone.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>June 2007</start_date>
  <primary_completion_date type="Actual">September 2007</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>AUCτ,ss (area under the concentration-time curve in plasma at steady state over a uniform dosing interval τ)</measure>
    <time_frame>up to 72 hours after last drug administration of each treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax,ss (maximum measured concentration in plasma at steady state over a uniform dosing interval τ)</measure>
    <time_frame>up to 72 hours after last drug administration of each treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Concentration of the analytes in plasma</measure>
    <time_frame>2, 4, and 12 hours after administration of the first dose of each treatment on day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>pre-dose concentration of the analytes in plasma immediately before the administration of the next dose</measure>
    <time_frame>pre-dose up to day 5 of each treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax,ss (time from last dosing to the maximum concentration of the analytes in plasma at steady state)</measure>
    <time_frame>up to 72 hours after last drug administration of each treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmin,ss (minimum concentration of the analytes in plasma at steady state over a uniform dosing interval τ)</measure>
    <time_frame>up to 72 hours after last drug administration of each treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cpre,ss (pre-dose concentration of the analytes in plasma immediately before the administration of the next dose at steady state)</measure>
    <time_frame>pre-dose up to day 5 of each treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cavg (average concentration of the analytes in plasma at steady state)</measure>
    <time_frame>up to 72 hours after last drug administration of each treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>λz,ss (terminal rate constant in plasma at steady state)</measure>
    <time_frame>up to 72 hours after last drug administration of each treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2, ss (terminal half-life of the analyte in plasma at steady state)</measure>
    <time_frame>up to 72 hours after last drug administration of each treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRTpo,ss (mean residence time of the analyte in the body at steady state after oral administration)</measure>
    <time_frame>up to 72 hours after last drug administration of each treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL/F,ss (apparent clearance of the analyte in plasma at steady state after extravascular multiple dose administration)</measure>
    <time_frame>up to 72 hours after last drug administration of each treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vz/F,ss (apparent volume of distribution of the analyte in plasma at steady state after extravascular multiple dose administration)</measure>
    <time_frame>up to 72 hours after last drug administration of each treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PTF (Peak-Trough Fluctuation)</measure>
    <time_frame>up to 72 hours after last drug administration of each treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-tz,ss (Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point)</measure>
    <time_frame>up to 72 hours after last drug administration of each treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>up to day 76</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically relevant changes in Vital Signs (Blood Pressure, Pulse rate)</measure>
    <time_frame>up to day 76</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically relevant changes in 12-lead electrocardiogram</measure>
    <time_frame>up to day 76</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically relevant changes in laboratory tests</measure>
    <time_frame>up to day 76</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of tolerability by the investigator on a 4-point scale</measure>
    <time_frame>Day 8 of each treatment</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">42</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Telmisartan + Ramipril</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>5 days qd</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Telmisartan</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>5 days qd</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ramipril</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>5 days qd</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Telmisartan</intervention_name>
    <arm_group_label>Telmisartan</arm_group_label>
    <arm_group_label>Telmisartan + Ramipril</arm_group_label>
    <other_name>Micardis®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ramipril</intervention_name>
    <arm_group_label>Ramipril</arm_group_label>
    <arm_group_label>Telmisartan + Ramipril</arm_group_label>
    <other_name>Delix®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy males and females according to the following criteria based upon a complete&#xD;
             medical history, including the physical examination, vital signs (Blood Pressure (BP),&#xD;
             Pulse Rate (PR)), 12-lead electrocardiogram (ECG), clinical laboratory tests&#xD;
&#xD;
          -  Age ≥18 and ≤55 years&#xD;
&#xD;
          -  Body mass index (BMI) ≥18.5 and ≤29.9 kg/m2&#xD;
&#xD;
          -  Signed and dated written informed consent prior to admission to the study in&#xD;
             accordance with Good Clinical Practice and the local legislation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any finding of the medical examination (including BP, PR and ECG) deviating from&#xD;
             normal and of clinical relevance&#xD;
&#xD;
          -  Any evidence of a clinically relevant concomitant disease&#xD;
&#xD;
          -  Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,&#xD;
             immunological or hormonal disorders&#xD;
&#xD;
          -  Surgery of the gastrointestinal tract (except appendectomy)&#xD;
&#xD;
          -  Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or&#xD;
             neurological disorders&#xD;
&#xD;
          -  History of relevant orthostatic hypotension, fainting spells or blackouts&#xD;
&#xD;
          -  Chronic or relevant acute infections&#xD;
&#xD;
          -  History of relevant allergy/hypersensitivity (including allergy to drug or its&#xD;
             excipients)&#xD;
&#xD;
          -  Intake of drugs with a long half-life (&gt; 24 hours) within at least one month or less&#xD;
             than 10 half-lives of the respective drug prior to administration or during the trial&#xD;
&#xD;
          -  Use of drugs which might reasonably influence the results of the trial (especially&#xD;
             unspecific inducing agents like St.John´s wort (Hypericum perforatum) or inhibitors&#xD;
             like cimetidine) or drugs that prolong the QT/QTc interval based on the knowledge at&#xD;
             the time of protocol preparation within 10 days prior to administration of trial drug&#xD;
             or during the trial&#xD;
&#xD;
          -  Participation in another trial with an investigational drug within two months prior to&#xD;
             administration or during the trial&#xD;
&#xD;
          -  Smoker (&gt; 10 cigarettes or &gt; 3 cigars or &gt; 3 pipes/day)&#xD;
&#xD;
          -  Alcohol abuse (more than 60 g/day) or inability to stop alcoholic beverages for 24&#xD;
             hours prior to dosing and up to the last sampling time point&#xD;
&#xD;
          -  Drug abuse&#xD;
&#xD;
          -  Blood donation (more than 100 mL within four weeks prior to administration of trial&#xD;
             drug or during the trial)&#xD;
&#xD;
          -  Excessive physical activities (within one week prior to administration of trial drug&#xD;
             or during the trial)&#xD;
&#xD;
          -  Any laboratory value outside the reference range that is of clinical relevance&#xD;
&#xD;
          -  Inability to comply with dietary regimen of trial site&#xD;
&#xD;
          -  A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a&#xD;
             QTc interval &gt;450 ms)&#xD;
&#xD;
          -  A history of additional risk factors for torsade de pointes (e.g., heart failure,&#xD;
             hyperkalaemia, hypokalemia, family history of Long QT Syndrome)&#xD;
&#xD;
          -  Any history of relevant low blood pressure&#xD;
&#xD;
          -  Supine blood pressure at screening of systolic &lt;110 mm Hg and diastolic &lt;60 mm Hg&#xD;
&#xD;
          -  History of urticaria&#xD;
&#xD;
          -  History of angioneurotic edema&#xD;
&#xD;
          -  Hereditary fructose intolerance&#xD;
&#xD;
          -  Salt and/or volume depletion&#xD;
&#xD;
        For female subjects:&#xD;
&#xD;
          -  Pregnancy or planning to become pregnant during the study or within 1 months of study&#xD;
             completion&#xD;
&#xD;
          -  Positive pregnancy test&#xD;
&#xD;
          -  Not willing or unable to use a reliable method of contraception such as implants,&#xD;
             injectables, combined oral contraceptives, sterilisation, intrauterine device, double&#xD;
             barrier method, sexual abstinence for at least 1 month, or vasectomised partner as&#xD;
             only method of contraception for at least 6 months prior to participation in the&#xD;
             trial, during and up to 1 month after completion/termination of the trial&#xD;
&#xD;
          -  Chronic use of oral contraception containing ethinyl estradiol as the only method of&#xD;
             contraception&#xD;
&#xD;
          -  Currently lactating&#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>
  <link>
    <url>http://trials.boehringer-ingelheim.com</url>
    <description>Related Info</description>
  </link>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>August 12, 2014</study_first_submitted>
  <study_first_submitted_qc>August 12, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2014</study_first_posted>
  <last_update_submitted>August 12, 2014</last_update_submitted>
  <last_update_submitted_qc>August 12, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 13, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Telmisartan</mesh_term>
    <mesh_term>Ramipril</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/NCT02215005
org study id: 1236.6
nct id: NCT02215005
lead sponsor: 
The main objective was to investigate the effect of concurrent dosing of 10 mg ramipril and
      80 mg telmisartan on the multiple-dose pharmacokinetics of telmisartan and ramipril.
      Therefore the relative bioavailability of telmisartan and ramipril given in combination was
      determined in comparison with either telmisartan or ramipril given alone.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: AUCτ,ss (area under the concentration-time curve in plasma at steady state over a uniform dosing interval τ)
time frame: up to 72 hours after last drug administration of each treatment
measure: Cmax,ss (maximum measured concentration in plasma at steady state over a uniform dosing interval τ)
time frame: up to 72 hours after last drug administration of each treatment
measure: Concentration of the analytes in plasma
time frame: 2, 4, and 12 hours after administration of the first dose of each treatment on day 1
measure: pre-dose concentration of the analytes in plasma immediately before the administration of the next dose
time frame: pre-dose up to day 5 of each treatment
measure: tmax,ss (time from last dosing to the maximum concentration of the analytes in plasma at steady state)
time frame: up to 72 hours after last drug administration of each treatment
measure: Cmin,ss (minimum concentration of the analytes in plasma at steady state over a uniform dosing interval τ)
time frame: up to 72 hours after last drug administration of each treatment
measure: Cpre,ss (pre-dose concentration of the analytes in plasma immediately before the administration of the next dose at steady state)
time frame: pre-dose up to day 5 of each treatment
measure: Cavg (average concentration of the analytes in plasma at steady state)
time frame: up to 72 hours after last drug administration of each treatment
measure: λz,ss (terminal rate constant in plasma at steady state)
time frame: up to 72 hours after last drug administration of each treatment
measure: t1/2, ss (terminal half-life of the analyte in plasma at steady state)
time frame: up to 72 hours after last drug administration of each treatment
measure: MRTpo,ss (mean residence time of the analyte in the body at steady state after oral administration)
time frame: up to 72 hours after last drug administration of each treatment
measure: CL/F,ss (apparent clearance of the analyte in plasma at steady state after extravascular multiple dose administration)
time frame: up to 72 hours after last drug administration of each treatment
measure: Vz/F,ss (apparent volume of distribution of the analyte in plasma at steady state after extravascular multiple dose administration)
time frame: up to 72 hours after last drug administration of each treatment
measure: PTF (Peak-Trough Fluctuation)
time frame: up to 72 hours after last drug administration of each treatment
measure: AUC0-tz,ss (Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point)
time frame: up to 72 hours after last drug administration of each treatment
measure: Number of patients with adverse events
time frame: up to day 76
measure: Number of patients with clinically relevant changes in Vital Signs (Blood Pressure, Pulse rate)
time frame: up to day 76
measure: Number of patients with clinically relevant changes in 12-lead electrocardiogram
time frame: up to day 76
measure: Number of patients with clinically relevant changes in laboratory tests
time frame: up to day 76
measure: Assessment of tolerability by the investigator on a 4-point scale
time frame: Day 8 of each treatment
arm group label: Telmisartan + Ramipril
arm group type: Experimental
description: 5 days qd
arm group label: Telmisartan
arm group type: Active Comparator
description: 5 days qd
arm group label: Ramipril
arm group type: Active Comparator
description: 5 days qd
intervention type: Drug
intervention name: Telmisartan
arm group label: Telmisartan
arm group label: Telmisartan + Ramipril
other name: Micardis®
intervention type: Drug
intervention name: Ramipril
arm group label: Ramipril
arm group label: Telmisartan + Ramipril
other name: Delix®
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: Telmisartan
mesh term: Ramipril