<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/NCT02231931</url>
  </required_header>
  <id_info>
    <org_study_id>352.2082</org_study_id>
    <secondary_id>2014-001940-40</secondary_id>
    <nct_id>NCT02231931</nct_id>
  </id_info>
  <brief_title>Drug-drug Interaction Between Digoxin, Furosemide, Metformin, and Rosuvastatin</brief_title>
  <official_title>Relative Bioavailability of a Single Oral Dose of Digoxin, Furosemide, Metformin, and Rosuvastatin Given Alone and All Together as a Cocktail, and Investigation of the Effect of Increased Doses of Metformin or Furosemide on Relative Bioavailability of the Other Cocktail Compounds in Healthy Male Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      To investigate the mutual interaction potential of digoxin, furosemide, metformin, and&#xD;
      rosuvastatin when given alone or together as a cocktail, and to investigate the effect of&#xD;
      high doses of metformin or furosemide on pharmacokinetics of the other cocktail compounds&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">January 2015</completion_date>
  <primary_completion_date type="Actual">January 2015</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>Digoxin, Metformin, Rosuvastatin: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point)</measure>
    <time_frame>up to 96 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Furosemide: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point)</measure>
    <time_frame>up to 36 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Furosemide: Cmax (maximum measured concentration of the analyte in plasma)</measure>
    <time_frame>up to 36 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Digoxin, Metformin, Rosuvastatin: Cmax (maximum measured concentration of the analyte in plasma)</measure>
    <time_frame>up to 96 hours</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Furosemide: AUC0-inf (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)</measure>
    <time_frame>up to 36 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Digoxin, Metformin, Rosuvastatin: AUC0-inf (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)</measure>
    <time_frame>up to 96 hours</time_frame>
  </secondary_outcome>
  <number_of_arms>7</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>A (Reference 1) Digoxin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 tablet as single dose, fasted</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B (Reference 2) Furosemide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>oral solution, as single dose, fasted</description>
  </arm_group>
  <arm_group>
    <arm_group_label>C (Reference 3) Metformin hydrochloride</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 film-coated tablet as single dose, fasted</description>
  </arm_group>
  <arm_group>
    <arm_group_label>D (Reference 4) Rosuvastatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 film-coated tablet as single dose, fasted</description>
  </arm_group>
  <arm_group>
    <arm_group_label>E (Test) 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Digoxin (1 tablet), Furosemide (0.5 mL oral solution), Metformin hydrochloride (1 film-coated tablet), Rosuvastatin (1 film-coated tablet), fasted</description>
  </arm_group>
  <arm_group>
    <arm_group_label>F (Test 2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Digoxin (1 tablet), Furosemide (0.5 mL oral solution), Metformin hydrochloride (2 film-coated tablets), Rosuvastatin (1 film-coated tablet), fasted</description>
  </arm_group>
  <arm_group>
    <arm_group_label>G (Test 3)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Digoxin (1 tablet), Furosemide (2.0 mL oral solution), Metformin hydrochloride (1 film-coated tablet), Rosuvastatin (1 film-coated tablet), fasted</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Digoxin</intervention_name>
    <description>single dose, fasted</description>
    <arm_group_label>A (Reference 1) Digoxin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rosuvastatin</intervention_name>
    <description>single dose, fasted</description>
    <arm_group_label>D (Reference 4) Rosuvastatin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Digoxin, Furosemide, Metformin hydrochloride, Rosuvastatin</intervention_name>
    <description>fasted</description>
    <arm_group_label>E (Test) 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Digoxin, Furosemide, Metformin hydrochloride, Rosuvastatin</intervention_name>
    <description>fasted</description>
    <arm_group_label>G (Test 3)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin hydrochloride</intervention_name>
    <description>single dose, fasted</description>
    <arm_group_label>C (Reference 3) Metformin hydrochloride</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Digoxin, Furosemide, Metformin hydrochloride, Rosuvastatin</intervention_name>
    <description>fasted</description>
    <arm_group_label>F (Test 2)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Furosemide</intervention_name>
    <description>single dose, fasted</description>
    <arm_group_label>B (Reference 2) Furosemide</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. Healthy male subjects according to the investigator´s assessment, based on a complete&#xD;
             medical history including a physical examination, vital signs (Blood Pressure, Pulse&#xD;
             Rate), 12-lead Electrocardiogram, and clinical laboratory tests&#xD;
&#xD;
          2. Age of 18 to 50 years (incl.)&#xD;
&#xD;
          3. Body Mass Index of 18.5 to 29.9 kg/m2 (incl.)&#xD;
&#xD;
          4. Signed and dated written informed consent prior to admission to the study in&#xD;
             accordance with Good Clinical Practice (GCP) and local legislation&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Any finding in the medical examination (including Blood Pressure, Pulse Rate, or&#xD;
             Electrocardiogram) is deviating from normal and judged as clinically relevant by the&#xD;
             investigator&#xD;
&#xD;
          2. Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg,&#xD;
             diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the&#xD;
             range of 50 to 90 bpm&#xD;
&#xD;
          3. Any laboratory value outside the reference range that the investigator considers to be&#xD;
             of clinical relevance&#xD;
&#xD;
          4. Any evidence of a concomitant disease judged as clinically relevant by the&#xD;
             investigator&#xD;
&#xD;
          5. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,&#xD;
             immunological, or hormonal disorders&#xD;
&#xD;
          6. Surgery of the gastrointestinal tract that could interfere with kinetics of the trial&#xD;
             medication (except appendectomy and simple hernia repair)&#xD;
&#xD;
          7. Diseases of the central nervous system (including but not limited to any kind of&#xD;
             seizures or stroke), and other relevant neurological or psychiatric disorders&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Boehringer Ingelheim</last_name>
    <role>Study Chair</role>
    <affiliation>Boehringer Ingelheim</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>352.2082.1 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Biberach</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>January 2015</verification_date>
  <study_first_submitted>September 3, 2014</study_first_submitted>
  <study_first_submitted_qc>September 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 4, 2014</study_first_posted>
  <last_update_submitted>January 22, 2015</last_update_submitted>
  <last_update_submitted_qc>January 22, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 26, 2015</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>Metformin</mesh_term>
    <mesh_term>Digoxin</mesh_term>
    <mesh_term>Furosemide</mesh_term>
    <mesh_term>Rosuvastatin Calcium</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/NCT02231931
org study id: 352.2082
secondary id: 2014-001940-40
nct id: NCT02231931
lead sponsor: 
To investigate the mutual interaction potential of digoxin, furosemide, metformin, and
      rosuvastatin when given alone or together as a cocktail, and to investigate the effect of
      high doses of metformin or furosemide on pharmacokinetics of the other cocktail compounds
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Digoxin, Metformin, Rosuvastatin: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point)
time frame: up to 96 hours
measure: Furosemide: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point)
time frame: up to 36 hours
measure: Furosemide: Cmax (maximum measured concentration of the analyte in plasma)
time frame: up to 36 hours
measure: Digoxin, Metformin, Rosuvastatin: Cmax (maximum measured concentration of the analyte in plasma)
time frame: up to 96 hours
measure: Furosemide: AUC0-inf (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
time frame: up to 36 hours
measure: Digoxin, Metformin, Rosuvastatin: AUC0-inf (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
time frame: up to 96 hours
arm group label: A (Reference 1) Digoxin
arm group type: Experimental
description: 1 tablet as single dose, fasted
arm group label: B (Reference 2) Furosemide
arm group type: Experimental
description: oral solution, as single dose, fasted
arm group label: C (Reference 3) Metformin hydrochloride
arm group type: Experimental
description: 1 film-coated tablet as single dose, fasted
arm group label: D (Reference 4) Rosuvastatin
arm group type: Experimental
description: 1 film-coated tablet as single dose, fasted
arm group label: E (Test) 1
arm group type: Experimental
description: Digoxin (1 tablet), Furosemide (0.5 mL oral solution), Metformin hydrochloride (1 film-coated tablet), Rosuvastatin (1 film-coated tablet), fasted
arm group label: F (Test 2)
arm group type: Experimental
description: Digoxin (1 tablet), Furosemide (0.5 mL oral solution), Metformin hydrochloride (2 film-coated tablets), Rosuvastatin (1 film-coated tablet), fasted
arm group label: G (Test 3)
arm group type: Experimental
description: Digoxin (1 tablet), Furosemide (2.0 mL oral solution), Metformin hydrochloride (1 film-coated tablet), Rosuvastatin (1 film-coated tablet), fasted
intervention type: Drug
intervention name: Digoxin
description: single dose, fasted
arm group label: A (Reference 1) Digoxin
intervention type: Drug
intervention name: Rosuvastatin
description: single dose, fasted
arm group label: D (Reference 4) Rosuvastatin
intervention type: Drug
intervention name: Digoxin, Furosemide, Metformin hydrochloride, Rosuvastatin
description: fasted
arm group label: E (Test) 1
intervention type: Drug
intervention name: Digoxin, Furosemide, Metformin hydrochloride, Rosuvastatin
description: fasted
arm group label: G (Test 3)
intervention type: Drug
intervention name: Metformin hydrochloride
description: single dose, fasted
arm group label: C (Reference 3) Metformin hydrochloride
intervention type: Drug
intervention name: Digoxin, Furosemide, Metformin hydrochloride, Rosuvastatin
description: fasted
arm group label: F (Test 2)
intervention type: Drug
intervention name: Furosemide
description: single dose, fasted
arm group label: B (Reference 2) Furosemide
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Boehringer Ingelheim
role: Study Chair
affiliation: Boehringer Ingelheim
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Metformin
mesh term: Digoxin
mesh term: Furosemide
mesh term: Rosuvastatin Calcium