<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/NCT02261103</url>
  </required_header>
  <id_info>
    <org_study_id>248.530</org_study_id>
    <nct_id>NCT02261103</nct_id>
  </id_info>
  <brief_title>Bioavailability of Increasing Pramipexole Doses of Oral Extended Release (ER) Tablets in Healthy Male Volunteers</brief_title>
  <official_title>A Multiple Dose Study With Increasing Pramipexole Doses (0.375 mg to 4.5 mg q.d.) of Oral Extended Release (ER) Tablets With a Three-way Cross Comparison of 4.5 mg Pramipexole ER q.d. Fasted Versus 4.5 mg Pramipexole ER q.d. Fed Versus 1.5 mg Pramipexole Immediate Release Tablets t.i.d. Fasted in Healthy Male Volunteers</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 objectives of the studies are:&#xD;
&#xD;
        -  To demonstrate similar total exposure between pramipexole ER fasted and pramipexole ER&#xD;
           fed after multiple administration of the highest daily dose of 4.5 mg q.d. and to reveal&#xD;
           any food effect leading to uncontrolled release&#xD;
&#xD;
        -  To investigate the relative bioavailability of the ER-formulation of pramipexole in&#xD;
           comparison to the IR-formulation at the highest daily dose of 4.5 mg after multiple&#xD;
           dosing&#xD;
&#xD;
        -  To demonstrate dose proportionality between the dose strengths of the pramipexole ER&#xD;
           formulation of 0.375, 0.75, 1.5, 3.0, and 4.5 mg after multiple daily (q.d.) dosing&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>April 2006</start_date>
  <primary_completion_date type="Actual">July 2006</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>Double</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ=0-24h (AUC0-24,ss) for ER</measure>
    <time_frame>up to 23 hours after drug application on day 5</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-24,ss for IR</measure>
    <time_frame>up to 23 hours after drug application on day 5</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum measured concentration of the analyte in plasma at steady state (Cmax)</measure>
    <time_frame>up to 23 hours after drug application on day 5</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the concentration-time curve of the analyte in plasma over the time interval 0 to 4h at steady state (AUC0-4,ss) for ER</measure>
    <time_frame>up to 4 hours after drug application</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ (Cmin,ss)</measure>
    <time_frame>up to 23 hours after drug application on day 5</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak-Trough Fluctuation (PTF)</measure>
    <time_frame>up to 23 hours after drug application on day 5</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from last dosing to the maximum concentration of the analyte in plasma at steady state over a uniform dosing interval τ (tmax,ss)</measure>
    <time_frame>up to 23 hours after drug application on day 5</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve of the analyte in plasma over the time interval 0 to 8 h at steady state (AUC0-8,ss)</measure>
    <time_frame>up to 8 hours after drug application</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Predose concentration of the analyte in plasma at steady state immediately before administration of the next dose (Cpre,ss)</measure>
    <time_frame>predose on days 1 to 5</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average concentration of the analyte in plasma at steady state (Cavg)</measure>
    <time_frame>up to 23 hours after drug application on day 5</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal half-life of the analyte in plasma at steady state (t1/2,ss)</measure>
    <time_frame>up to 23 hours after drug application on day 5</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean residence time of the analyte in the body at steady state after p.o. administration (MRTpo,ss)</measure>
    <time_frame>up to 23 hours after drug application on day 5</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent clearance of the analyte in plasma at steady state after extravascular multiple dose administration (CL/F,ss)</measure>
    <time_frame>up to 23 hours after drug application on day 5</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal clearance of the analyte at steady state determined over the dosing interval τ (CLR,ss)</measure>
    <time_frame>up to 23 hours after drug application on day 5</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution during the terminal phase λz at steady state following extravascular administration (Vz/F,ss)</measure>
    <time_frame>up to 23 hours after drug application on day 5</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Amount of analyte that is eliminated in urine at steady state from the time point 0 to time point 24 (Ae0-24,ss)</measure>
    <time_frame>up to 23 hours after drug application on day 5</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Amount of analyte that is eliminated in urine at steady state from the time point 0 to time point 8 (Ae0-8,ss) for IR</measure>
    <time_frame>up to 8 hours after drug application on day 5</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with adverse events</measure>
    <time_frame>up to 7 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with clinically relevant changes in vital signs</measure>
    <time_frame>up to 7 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with clinically relevant changes in laboratory parameters</measure>
    <time_frame>up to 7 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of global tolerability by investigator on a 4-point scale</measure>
    <time_frame>day 5 of each visit</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">39</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Pramipexole IR, fasted</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Pramipexole immediate release (IR) tablets</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pramipexole ER, fasted</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pramipexole extended release (ER) tablets</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pramipexole ER, fed</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pramipexole extended release tablets with a high-fat meal 30 min before drug administration</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pramipexole ER tablets</intervention_name>
    <arm_group_label>Pramipexole ER, fasted</arm_group_label>
    <arm_group_label>Pramipexole ER, fed</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pramipexole IR tablets</intervention_name>
    <arm_group_label>Pramipexole IR, fasted</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo matching Pramipexole ER tablets</intervention_name>
    <arm_group_label>Pramipexole IR, fasted</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo matching Pramipexole IR tablets</intervention_name>
    <arm_group_label>Pramipexole ER, fasted</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard high-fat breakfast</intervention_name>
    <arm_group_label>Pramipexole ER, fed</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All participants in the study should be healthy males&#xD;
&#xD;
          -  Age range from 21 to 50 years&#xD;
&#xD;
          -  Body mass index (BMI) be within 18.5 to 29.9 kg/m2&#xD;
&#xD;
          -  In accordance with Good Clinical Practice and the local legislation all volunteers&#xD;
             will have given their written informed consent prior to admission to the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any finding of the medical examination (including blood pressure, pulse rate and ECG)&#xD;
             deviating from normal and of clinical relevance&#xD;
&#xD;
          -  Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,&#xD;
             immunological or hormonal disorders&#xD;
&#xD;
          -  Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or&#xD;
             neurological disorders&#xD;
&#xD;
          -  History of orthostatic hypotension, fainting spells or blackouts&#xD;
&#xD;
          -  Chronic or relevant acute infections&#xD;
&#xD;
          -  History of allergy/hypersensitivity (including drug allergy) which is deemed relevant&#xD;
             to the trial as judged by the investigator&#xD;
&#xD;
          -  Intake of drugs with a long half-life (&gt; 24:00 hours) within at least one month or&#xD;
             less than ten half-lives of the respective drug before enrolment in the study or&#xD;
             during the study&#xD;
&#xD;
          -  Use of any drugs which might influence the results of the trial up to 7 days prior to&#xD;
             enrolment in the study or during the study&#xD;
&#xD;
          -  Participation in another trial with an investigational drug (≤ one month 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;
          -  Inability to refrain from smoking on in-house trial days&#xD;
&#xD;
          -  Alcohol abuse (&gt; 40 g/day)&#xD;
&#xD;
          -  Drug abuse&#xD;
&#xD;
          -  Blood donation (≥ 100 mL within four weeks prior to administration or during the&#xD;
             trial)&#xD;
&#xD;
          -  Any laboratory value outside the clinically accepted reference range&#xD;
&#xD;
          -  Excessive physical activities within the last week before the trial or during the&#xD;
             trial&#xD;
&#xD;
          -  Hypersensitivity to pramipexole, or other dopamine agonists&#xD;
&#xD;
          -  Supine blood pressure at screening of systolic &lt; 110 mmHg and diastolic &lt; 60 mmHg&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>50 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>October 2014</verification_date>
  <study_first_submitted>October 9, 2014</study_first_submitted>
  <study_first_submitted_qc>October 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2014</study_first_posted>
  <last_update_submitted>October 9, 2014</last_update_submitted>
  <last_update_submitted_qc>October 9, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 10, 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>Pramipexole</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/NCT02261103
org study id: 248.530
nct id: NCT02261103
lead sponsor: 
The objectives of the studies are:

        -  To demonstrate similar total exposure between pramipexole ER fasted and pramipexole ER
           fed after multiple administration of the highest daily dose of 4.5 mg q.d. and to reveal
           any food effect leading to uncontrolled release

        -  To investigate the relative bioavailability of the ER-formulation of pramipexole in
           comparison to the IR-formulation at the highest daily dose of 4.5 mg after multiple
           dosing

        -  To demonstrate dose proportionality between the dose strengths of the pramipexole ER
           formulation of 0.375, 0.75, 1.5, 3.0, and 4.5 mg after multiple daily (q.d.) dosing
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double
measure: Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ=0-24h (AUC0-24,ss) for ER
time frame: up to 23 hours after drug application on day 5
measure: AUC0-24,ss for IR
time frame: up to 23 hours after drug application on day 5
measure: Maximum measured concentration of the analyte in plasma at steady state (Cmax)
time frame: up to 23 hours after drug application on day 5
measure: Area under the concentration-time curve of the analyte in plasma over the time interval 0 to 4h at steady state (AUC0-4,ss) for ER
time frame: up to 4 hours after drug application
measure: Minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ (Cmin,ss)
time frame: up to 23 hours after drug application on day 5
measure: Peak-Trough Fluctuation (PTF)
time frame: up to 23 hours after drug application on day 5
measure: Time from last dosing to the maximum concentration of the analyte in plasma at steady state over a uniform dosing interval τ (tmax,ss)
time frame: up to 23 hours after drug application on day 5
measure: Area under the concentration-time curve of the analyte in plasma over the time interval 0 to 8 h at steady state (AUC0-8,ss)
time frame: up to 8 hours after drug application
measure: Predose concentration of the analyte in plasma at steady state immediately before administration of the next dose (Cpre,ss)
time frame: predose on days 1 to 5
measure: Average concentration of the analyte in plasma at steady state (Cavg)
time frame: up to 23 hours after drug application on day 5
measure: Terminal half-life of the analyte in plasma at steady state (t1/2,ss)
time frame: up to 23 hours after drug application on day 5
measure: Mean residence time of the analyte in the body at steady state after p.o. administration (MRTpo,ss)
time frame: up to 23 hours after drug application on day 5
measure: Apparent clearance of the analyte in plasma at steady state after extravascular multiple dose administration (CL/F,ss)
time frame: up to 23 hours after drug application on day 5
measure: Renal clearance of the analyte at steady state determined over the dosing interval τ (CLR,ss)
time frame: up to 23 hours after drug application on day 5
measure: Apparent volume of distribution during the terminal phase λz at steady state following extravascular administration (Vz/F,ss)
time frame: up to 23 hours after drug application on day 5
measure: Amount of analyte that is eliminated in urine at steady state from the time point 0 to time point 24 (Ae0-24,ss)
time frame: up to 23 hours after drug application on day 5
measure: Amount of analyte that is eliminated in urine at steady state from the time point 0 to time point 8 (Ae0-8,ss) for IR
time frame: up to 8 hours after drug application on day 5
measure: Number of subjects with adverse events
time frame: up to 7 days after last drug administration
measure: Number of subjects with clinically relevant changes in vital signs
time frame: up to 7 days after last drug administration
measure: Number of subjects with clinically relevant changes in laboratory parameters
time frame: up to 7 days after last drug administration
measure: Assessment of global tolerability by investigator on a 4-point scale
time frame: day 5 of each visit
arm group label: Pramipexole IR, fasted
arm group type: Active Comparator
description: Pramipexole immediate release (IR) tablets
arm group label: Pramipexole ER, fasted
arm group type: Experimental
description: Pramipexole extended release (ER) tablets
arm group label: Pramipexole ER, fed
arm group type: Experimental
description: Pramipexole extended release tablets with a high-fat meal 30 min before drug administration
intervention type: Drug
intervention name: Pramipexole ER tablets
arm group label: Pramipexole ER, fasted
arm group label: Pramipexole ER, fed
intervention type: Drug
intervention name: Pramipexole IR tablets
arm group label: Pramipexole IR, fasted
intervention type: Drug
intervention name: Placebo matching Pramipexole ER tablets
arm group label: Pramipexole IR, fasted
intervention type: Drug
intervention name: Placebo matching Pramipexole IR tablets
arm group label: Pramipexole ER, fasted
intervention type: Other
intervention name: Standard high-fat breakfast
arm group label: Pramipexole ER, fed
criteria: 
gender: Male
minimum age: 21 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: Pramipexole