<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/NCT03307252</url>
  </required_header>
  <id_info>
    <org_study_id>0352-2100</org_study_id>
    <secondary_id>2017-001549-29</secondary_id>
    <nct_id>NCT03307252</nct_id>
  </id_info>
  <brief_title>This Study Tests the Effect of Certain Medicines on the Transport of Other Medicines in the Body of Healthy Men</brief_title>
  <official_title>The Effect of Potent Inhibitors of Drug Transporters (Verapamil, Rifampin, Cimetidine, Probenecid) on Pharmacokinetics of a Transporter Probe Drug Cocktail Consisting of Digoxin, Furosemide, Metformin and Rosuvastatin (an Open-label, Randomised, Crossover Trial in Three Parts)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this trial is to investigate the relative bioavailabilities of&#xD;
      digoxin, furosemide, metformin and rosuvastatin given as a cocktail alone and as a cocktail&#xD;
      together with the following drug transporter inhibitors:&#xD;
&#xD;
      Part 1: verapamil (P-gp) and rifampin (OATP1B1/1B3) Part 2: cimetidine (OCT2/MATE) Part 3:&#xD;
      probenecid (OAT1/3) The secondary objective is to investigate other potential changes in&#xD;
      pharmacokinetics (e.g. in clearance, volume of distribution, etc.) of digoxin, furosemide,&#xD;
      metformin and rosuvastatin given as a cocktail alone and as a cocktail together with the&#xD;
      inhibitors describe above.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 25, 2017</start_date>
  <completion_date type="Actual">May 2, 2018</completion_date>
  <primary_completion_date type="Actual">May 2, 2018</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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Verapamil + R1 (T1) vs. R1)</measure>
    <time_frame>Samples were taken within 0:20 hour:minutes (hh:mm) prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.</time_frame>
    <description>AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. Geometric mean (gMean) presented here is an adjusted gMean and standard error (SE) presented is a geometric SE (gSE).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Rifampin + R1 (T2) vs. R1)</measure>
    <time_frame>Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.</time_frame>
    <description>AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Cimetidine + R1 (T3) vs. R1)</measure>
    <time_frame>Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.</time_frame>
    <description>AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Probenecid + R1 (T4) vs. R1)</measure>
    <time_frame>Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.</time_frame>
    <description>AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T1 vs. R1)</measure>
    <time_frame>Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.</time_frame>
    <description>Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T2 vs. R1)</measure>
    <time_frame>Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.</time_frame>
    <description>Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T3 vs. R1)</measure>
    <time_frame>Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.</time_frame>
    <description>Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T4 vs. R1)</measure>
    <time_frame>Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.</time_frame>
    <description>Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T1 vs. R1)</measure>
    <time_frame>Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.</time_frame>
    <description>AUC0-∞, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 extrapolated to infinity is presented. AUC0-∞ not displayed for Digoxin analyte as precision was considered non-sufficient. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T2 vs. R1)</measure>
    <time_frame>Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.</time_frame>
    <description>AUC0-∞, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 extrapolated to infinity is presented. AUC0-∞ not displayed for Digoxin analyte as precision was considered non-sufficient. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T3 vs. R1)</measure>
    <time_frame>Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.</time_frame>
    <description>AUC0-∞, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 extrapolated to infinity is presented. AUC0-∞ not displayed for Digoxin analyte as precision was considered non-sufficient. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T4 vs. R1)</measure>
    <time_frame>Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.</time_frame>
    <description>AUC0-∞, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 extrapolated to infinity is presented. AUC0-∞ not displayed for Digoxin analyte as precision was considered non-sufficient. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
  </secondary_outcome>
  <number_of_arms>9</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Treatment Reference 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Reference 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Reference 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment 5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment 6</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Digoxin</intervention_name>
    <description>Tablet</description>
    <arm_group_label>Treatment 1</arm_group_label>
    <arm_group_label>Treatment 2</arm_group_label>
    <arm_group_label>Treatment 3</arm_group_label>
    <arm_group_label>Treatment 4</arm_group_label>
    <arm_group_label>Treatment Reference 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Furosemide</intervention_name>
    <description>Oral solution</description>
    <arm_group_label>Treatment 1</arm_group_label>
    <arm_group_label>Treatment 2</arm_group_label>
    <arm_group_label>Treatment 3</arm_group_label>
    <arm_group_label>Treatment 4</arm_group_label>
    <arm_group_label>Treatment 6</arm_group_label>
    <arm_group_label>Treatment Reference 1</arm_group_label>
    <arm_group_label>Treatment Reference 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>Oral solution</description>
    <arm_group_label>Treatment 1</arm_group_label>
    <arm_group_label>Treatment 2</arm_group_label>
    <arm_group_label>Treatment 3</arm_group_label>
    <arm_group_label>Treatment 4</arm_group_label>
    <arm_group_label>Treatment 5</arm_group_label>
    <arm_group_label>Treatment Reference 1</arm_group_label>
    <arm_group_label>Treatment Reference 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rosuvastatin</intervention_name>
    <description>Film-coated tablet</description>
    <arm_group_label>Treatment 1</arm_group_label>
    <arm_group_label>Treatment 2</arm_group_label>
    <arm_group_label>Treatment 3</arm_group_label>
    <arm_group_label>Treatment 4</arm_group_label>
    <arm_group_label>Treatment Reference 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Verapamil</intervention_name>
    <description>Film-coated tablet</description>
    <arm_group_label>Treatment 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rifampin</intervention_name>
    <description>Film-coated tablet</description>
    <arm_group_label>Treatment 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cimetidine</intervention_name>
    <description>Tablet</description>
    <arm_group_label>Treatment 3</arm_group_label>
    <arm_group_label>Treatment 5</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Probenecid</intervention_name>
    <description>Tablet</description>
    <arm_group_label>Treatment 4</arm_group_label>
    <arm_group_label>Treatment 6</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male subjects according to the investigator's assessment, based on a complete&#xD;
             medical history including a physical examination, vital signs (Blood Pressure (BP),&#xD;
             Pulse Rate (PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests&#xD;
&#xD;
          -  Age of 18 to 55 years (incl.)&#xD;
&#xD;
          -  Body Mass Index (BMI) of 18.5 to 29.9 kg/m2 (incl.)&#xD;
&#xD;
          -  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;
          -  Any finding in the medical examination (including Blood Pressure (BP), Pulse Rate (PR)&#xD;
             or Electrocardiogram (ECG)) is deviating from normal and judged as clinically relevant&#xD;
             by the investigator&#xD;
&#xD;
          -  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;
          -  Any laboratory value outside the reference range that the investigator considers to be&#xD;
             of clinical relevance&#xD;
&#xD;
          -  Any evidence of a concomitant disease judged as clinically relevant by the&#xD;
             investigator&#xD;
&#xD;
          -  Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,&#xD;
             immunological or hormonal disorders&#xD;
&#xD;
          -  Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with&#xD;
             the pharmacokinetics of the trial medication (except appendectomy and simple hernia&#xD;
             repair)&#xD;
&#xD;
          -  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;
&#xD;
          -  History of relevant orthostatic hypotension, fainting spells, or blackouts&#xD;
&#xD;
          -  Chronic or relevant acute infections&#xD;
&#xD;
          -  History of relevant allergy or hypersensitivity (including allergy to the trial&#xD;
             medication or its excipients, sulphonamides, or cardiac glycosides)&#xD;
&#xD;
          -  Use of drugs within 30 days prior to administration of trial medication if that might&#xD;
             reasonably influence the results of the trial (incl. QT/QTc interval prolongation)&#xD;
&#xD;
          -  Participation in another trial where an investigational drug has been administered&#xD;
             within 60 days prior to planned administration of trial medication, or current&#xD;
             participation in another trial involving administration of investigational drug&#xD;
&#xD;
          -  Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)&#xD;
&#xD;
          -  Inability to refrain from smoking on specified trial days&#xD;
&#xD;
          -  Alcohol abuse (consumption of more than 24 g per day for males)&#xD;
&#xD;
          -  Drug abuse or positive drug screening&#xD;
&#xD;
          -  Blood donation of more than 100 mL within 30 days prior to administration of trial&#xD;
             medication or intended donation during the trial&#xD;
&#xD;
          -  Intention to perform excessive physical activities within one week prior to&#xD;
             administration of trial medication or during the trial&#xD;
&#xD;
          -  Inability to comply with dietary regimen of trial site&#xD;
&#xD;
          -  Subject is assessed as unsuitable for inclusion by the investigator, for instance,&#xD;
             because considered not able to understand and comply with study requirements, or has a&#xD;
             condition that would not allow safe participation in the study&#xD;
&#xD;
          -  Male subjects with Women of child bearing potential (WOCBP) partner who are unwilling&#xD;
             to use male contraception (condom or sexual abstinence) from the first administration&#xD;
             of trial medication until 30 days after last administration of trial medication&#xD;
&#xD;
          -  Hypokalemia, hypomagnesemia, or hypercalcemia&#xD;
&#xD;
          -  PQ interval greater than 220 ms in the Electrocardiogram (ECG) at screening&#xD;
&#xD;
          -  Marked conductivity disorders (e.g. sinu-atrial blocks of II° or III°)&#xD;
&#xD;
          -  Myopathy&#xD;
&#xD;
          -  Hereditary galactose or fructose intolerance, lactase deficiency, or glucose-galactose&#xD;
             malabsorption&#xD;
&#xD;
          -  History of nephrolithiasis&#xD;
&#xD;
          -  Gout or clinically relevant elevation of uric acid&#xD;
&#xD;
          -  Creatinine clearance (according to CKD EPI formula) is lower than 80 ml/min&#xD;
&#xD;
          -  Further exclusion criteria apply&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>CTC North GmbH &amp; Co. KG, Hamburg</name>
      <address>
        <city>Hamburg</city>
        <zip>20251</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <link>
    <url>http://trials.boehringer-ingelheim.com/</url>
    <description>Related Info</description>
  </link>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>October 6, 2017</study_first_submitted>
  <study_first_submitted_qc>October 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 11, 2017</study_first_posted>
  <results_first_submitted>April 30, 2019</results_first_submitted>
  <results_first_submitted_qc>April 30, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">July 12, 2019</results_first_posted>
  <last_update_submitted>April 30, 2019</last_update_submitted>
  <last_update_submitted_qc>April 30, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 12, 2019</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>Rifampin</mesh_term>
    <mesh_term>Probenecid</mesh_term>
    <mesh_term>Digoxin</mesh_term>
    <mesh_term>Verapamil</mesh_term>
    <mesh_term>Furosemide</mesh_term>
    <mesh_term>Cimetidine</mesh_term>
    <mesh_term>Rosuvastatin Calcium</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 7, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/52/NCT03307252/SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 1, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/52/NCT03307252/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The trial consisted of 3 parts investigating different drug transporter inhibitors. All parts of the trial were performed in healthy male participants in a randomised, open-label, three-way (Part 1) or four-way (Part 2 and 3) crossover design.</recruitment_details>
      <pre_assignment_details>All participants were screened for eligibility to participate in the trial. Participants were not to be randomised to trial treatment if any of the in- or exclusion criteria were violated at screening.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Cocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)</title>
          <description>In trial part 1 participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 milliliter (mL) of water in period 1. R1 is a drug cocktail that contains a single dose of each, 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by a single dose of 120 mg Verapamil orally with 240 mL of water at 1 hour (h) prior to R1 which is administered with 280 mL of water in period 2. In period 3 participants were administered a single dose of 600 mg Rifampin film-coated tablet with 280 mL of water together with R1. Treatment periods were separated by a wash-out period of 13 days.</description>
        </group>
        <group group_id="P2">
          <title>(Verapamil + R1)/ (Rifampin + R1)/ R1</title>
          <description>In trial part 1 participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 h prior to R1 which is administered with 280 mL of water in period 1. Followed by a single dose of 600 mg Rifampin film-coated tablet orally with 280 mL of water together with R1 in period 2. In period 3 participants were administered a single dose of R1 with 280 milliliter (mL) of water. R1 is a drug cocktail that contains a single dose of each, 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Treatment periods were separated by a wash-out period of 13 days.</description>
        </group>
        <group group_id="P3">
          <title>(Rifampin + R1)/ R1/ (Verapamil + R1)</title>
          <description>In trial part 1 participants were administered a single dose of 600 mg Rifampin film-coated tablet orally with 280 mL of water together with R1 in period 1. Followed by a single dose of R1 with 280 mL of water in period 2. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. In period 3 participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 hour (h) prior to the R1 which is administered with 280 mL of water. Treatment periods were separated by a wash-out period of 13 days.</description>
        </group>
        <group group_id="P4">
          <title>R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)</title>
          <description>In trial part 2 participants were administered single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains a single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 2. Followed by 400 mg Cimetidine 1 orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 3. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to therapeutic dose of 500mg of Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after metformin (Day 2) in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.</description>
        </group>
        <group group_id="P5">
          <title>Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)</title>
          <description>In trial part 2 participants were administered single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 1. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after metformin (Day 2) in period 2. Followed by a single dose of R1 with 280 mL of water in period 3. R1 is a drug cocktail that contains single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by 400 mg Cimetidine 1 orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.</description>
        </group>
        <group group_id="P6">
          <title>(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin</title>
          <description>In trial part 2 participants were administered 400 mg Cimetidine 1 tablet orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 1. Followed by single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in period 2. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after Metformin (Day 2) in period 3. Followed by single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.</description>
        </group>
        <group group_id="P7">
          <title>(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1</title>
          <description>In trial part 2 participants were administered 400 mg Cimetidine 1 tablet orally at 1 h prior to Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after Metformin (Day 2) in period 1. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 2. Followed by single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 3. Followed by single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.</description>
        </group>
        <group group_id="P8">
          <title>R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)</title>
          <description>In trial part 3 participants were administered single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 2. Followed by 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 3. Followed by 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 4. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.</description>
        </group>
        <group group_id="P9">
          <title>Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)</title>
          <description>In trial part 3 participants were administered single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 1. Followed by 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 2. Followed by single dose of R1 which is administered with 280 milliliter (mL) of water in period 3. R1 is a drug cocktail that contains single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 4. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.</description>
        </group>
        <group group_id="P10">
          <title>(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide</title>
          <description>In trial part 3 participants were administered 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 1. Followed by single dose of R1 which is administered with 280 mL of water in period 2. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 3. Followed by single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 4. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.</description>
        </group>
        <group group_id="P11">
          <title>(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1</title>
          <description>In trial part 3 participants were administered 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 1. Followed by 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 2. Followed by single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 3. Followed by single dose of R1 which is administered with 280 milliliter (mL) of water in period 4. R1 is a drug cocktail that contains a single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Part 1, Period 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4">Participants randomised in Part 1</participants>
                <participants group_id="P2" count="4">Participants randomised in Part 1</participants>
                <participants group_id="P3" count="4">Participants randomised in Part 1</participants>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Part 1, Washout Period 1 (13 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Part 1, Period 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4">Participants randomised in Part 1</participants>
                <participants group_id="P2" count="4">Participants randomised in Part 1</participants>
                <participants group_id="P3" count="4">Participants randomised in Part 1</participants>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Part 1, Washout Period 2 (13 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Part 1, Period 3</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4">Participants randomised in Part 1</participants>
                <participants group_id="P2" count="4">Participants randomised in Part 1</participants>
                <participants group_id="P3" count="4">Participants randomised in Part 1</participants>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Part 2, Period 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="4">Participants randomized in Part 2</participants>
                <participants group_id="P5" count="4">Participants randomized in Part 2</participants>
                <participants group_id="P6" count="4">Participants randomized in Part 2</participants>
                <participants group_id="P7" count="5">Participants randomized in Part 2</participants>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="4"/>
                <participants group_id="P6" count="3"/>
                <participants group_id="P7" count="5"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="1"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Treatment not received</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="1"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Part 2, Washout Period 1 (7 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="4"/>
                <participants group_id="P6" count="3"/>
                <participants group_id="P7" count="5"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="4"/>
                <participants group_id="P6" count="3"/>
                <participants group_id="P7" count="5"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Part 2, Period 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="4"/>
                <participants group_id="P6" count="3"/>
                <participants group_id="P7" count="5"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="4"/>
                <participants group_id="P6" count="3"/>
                <participants group_id="P7" count="5"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Part 2, Washout Period 2 (7 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="4"/>
                <participants group_id="P6" count="3"/>
                <participants group_id="P7" count="5"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="4"/>
                <participants group_id="P6" count="3"/>
                <participants group_id="P7" count="5"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Part 2, Period 3</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="4"/>
                <participants group_id="P6" count="3"/>
                <participants group_id="P7" count="5"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="3"/>
                <participants group_id="P6" count="3"/>
                <participants group_id="P7" count="5"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Other than listed</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Part 2, Washout Period 3 (7 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="3"/>
                <participants group_id="P6" count="3"/>
                <participants group_id="P7" count="5"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="3"/>
                <participants group_id="P6" count="3"/>
                <participants group_id="P7" count="4"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="1"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Part 2, Period 4</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="3"/>
                <participants group_id="P6" count="3"/>
                <participants group_id="P7" count="5"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="3"/>
                <participants group_id="P6" count="3"/>
                <participants group_id="P7" count="4"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="1"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Other than listed</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="1"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Part 3, Period 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="4"/>
                <participants group_id="P9" count="4"/>
                <participants group_id="P10" count="4"/>
                <participants group_id="P11" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="4">Participants randomized in Part 3</participants>
                <participants group_id="P9" count="4">Participants randomized in Part 3</participants>
                <participants group_id="P10" count="4">Participants randomized in Part 3</participants>
                <participants group_id="P11" count="4">Participants randomized in Part 3</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Part 3, Washout Period 1 (7 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="4"/>
                <participants group_id="P9" count="4"/>
                <participants group_id="P10" count="4"/>
                <participants group_id="P11" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="4"/>
                <participants group_id="P9" count="4"/>
                <participants group_id="P10" count="4"/>
                <participants group_id="P11" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Part 3, Period 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="4"/>
                <participants group_id="P9" count="4"/>
                <participants group_id="P10" count="4"/>
                <participants group_id="P11" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="4"/>
                <participants group_id="P9" count="4"/>
                <participants group_id="P10" count="4"/>
                <participants group_id="P11" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Part 3, Washout Period 2 (7 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="4"/>
                <participants group_id="P9" count="4"/>
                <participants group_id="P10" count="4"/>
                <participants group_id="P11" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="4"/>
                <participants group_id="P9" count="4"/>
                <participants group_id="P10" count="4"/>
                <participants group_id="P11" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Part 3, Period 3</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="4"/>
                <participants group_id="P9" count="4"/>
                <participants group_id="P10" count="4"/>
                <participants group_id="P11" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="4"/>
                <participants group_id="P9" count="4"/>
                <participants group_id="P10" count="4"/>
                <participants group_id="P11" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Part 3, Washout Period 3 (7 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="4"/>
                <participants group_id="P9" count="4"/>
                <participants group_id="P10" count="4"/>
                <participants group_id="P11" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="4"/>
                <participants group_id="P9" count="4"/>
                <participants group_id="P10" count="4"/>
                <participants group_id="P11" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Treatment not received due to AE</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Part 3, Period 4</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="4"/>
                <participants group_id="P9" count="4"/>
                <participants group_id="P10" count="4"/>
                <participants group_id="P11" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="4"/>
                <participants group_id="P9" count="4"/>
                <participants group_id="P10" count="4"/>
                <participants group_id="P11" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Treated set (TS): All subjects who were dispended study medication and were documented to have taken at least 1 dose of study medication.</population>
      <group_list>
        <group group_id="B1">
          <title>Cocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)</title>
          <description>In trial part 1 participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 milliliter (mL) of water in period 1. R1 is a drug cocktail that contains a single dose of each, 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by a single dose of 120 mg Verapamil orally with 240 mL of water at 1 hour (h) prior to R1 which is administered with 280 mL of water in period 2. In period 3 participants were administered a single dose of 600 mg Rifampin film-coated tablet with 280 mL of water together with R1. Treatment periods were separated by a wash-out period of 13 days.</description>
        </group>
        <group group_id="B2">
          <title>(Verapamil + R1)/ (Rifampin + R1)/ R1</title>
          <description>In trial part 1 participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 h prior to R1 which is administered with 280 mL of water in period 1. Followed by a single dose of 600 mg Rifampin film-coated tablet orally with 280 mL of water together with R1 in period 2. In period 3 participants were administered a single dose of R1 with 280 milliliter (mL) of water. R1 is a drug cocktail that contains a single dose of each, 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Treatment periods were separated by a wash-out period of 13 days.</description>
        </group>
        <group group_id="B3">
          <title>(Rifampin + R1)/ R1/ (Verapamil + R1)</title>
          <description>In trial part 1 participants were administered a single dose of 600 mg Rifampin film-coated tablet orally with 280 mL of water together with R1 in period 1. Followed by a single dose of R1 with 280 mL of water in period 2. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. In period 3 participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 hour (h) prior to the R1 which is administered with 280 mL of water. Treatment periods were separated by a wash-out period of 13 days.</description>
        </group>
        <group group_id="B4">
          <title>R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)</title>
          <description>In trial part 2 participants were administered single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains a single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 2. Followed by 400 mg Cimetidine 1 orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 3. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to therapeutic dose of 500mg of Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after metformin (Day 2) in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.</description>
        </group>
        <group group_id="B5">
          <title>Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)</title>
          <description>In trial part 2 participants were administered single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 1. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after metformin (Day 2) in period 2. Followed by a single dose of R1 with 280 mL of water in period 3. R1 is a drug cocktail that contains single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by 400 mg Cimetidine 1 orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.</description>
        </group>
        <group group_id="B6">
          <title>(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin</title>
          <description>In trial part 2 participants were administered 400 mg Cimetidine 1 tablet orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 1. Followed by single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in period 2. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after Metformin (Day 2) in period 3. Followed by single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.</description>
        </group>
        <group group_id="B7">
          <title>(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1</title>
          <description>In trial part 2 participants were administered 400 mg Cimetidine 1 tablet orally at 1 h prior to Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after Metformin (Day 2) in period 1. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 2. Followed by single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 3. Followed by single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.</description>
        </group>
        <group group_id="B8">
          <title>R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)</title>
          <description>In trial part 3 participants were administered single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 2. Followed by 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 3. Followed by 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 4. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.</description>
        </group>
        <group group_id="B9">
          <title>Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)</title>
          <description>In trial part 3 participants were administered single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 1. Followed by 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 2. Followed by single dose of R1 which is administered with 280 milliliter (mL) of water in period 3. R1 is a drug cocktail that contains single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 4. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.</description>
        </group>
        <group group_id="B10">
          <title>(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide</title>
          <description>In trial part 3 participants were administered 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 1. Followed by single dose of R1 which is administered with 280 mL of water in period 2. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 3. Followed by single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 4. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.</description>
        </group>
        <group group_id="B11">
          <title>(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1</title>
          <description>In trial part 3 participants were administered 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 1. Followed by 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 2. Followed by single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 3. Followed by single dose of R1 which is administered with 280 milliliter (mL) of water in period 4. R1 is a drug cocktail that contains a single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.</description>
        </group>
        <group group_id="B12">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="4"/>
            <count group_id="B2" value="4"/>
            <count group_id="B3" value="4"/>
            <count group_id="B4" value="4"/>
            <count group_id="B5" value="4"/>
            <count group_id="B6" value="4"/>
            <count group_id="B7" value="5"/>
            <count group_id="B8" value="4"/>
            <count group_id="B9" value="4"/>
            <count group_id="B10" value="4"/>
            <count group_id="B11" value="4"/>
            <count group_id="B12" value="45"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>Part 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30.0" spread="6.8"/>
                    <measurement group_id="B2" value="51.5" spread="1.3"/>
                    <measurement group_id="B3" value="36.3" spread="10.6"/>
                    <measurement group_id="B4" value="32.8" spread="10.2"/>
                    <measurement group_id="B5" value="38.3" spread="13.1"/>
                    <measurement group_id="B6" value="35.3" spread="11.1"/>
                    <measurement group_id="B7" value="41.6" spread="10.5"/>
                    <measurement group_id="B8" value="29.3" spread="7.9"/>
                    <measurement group_id="B9" value="30.0" spread="8.8"/>
                    <measurement group_id="B10" value="33.0" spread="13.2"/>
                    <measurement group_id="B11" value="43.5" spread="8.1"/>
                    <measurement group_id="B12" value="36.6" spread="10.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                    <measurement group_id="B10" value="0"/>
                    <measurement group_id="B11" value="0"/>
                    <measurement group_id="B12" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="4"/>
                    <measurement group_id="B7" value="5"/>
                    <measurement group_id="B8" value="4"/>
                    <measurement group_id="B9" value="4"/>
                    <measurement group_id="B10" value="4"/>
                    <measurement group_id="B11" value="4"/>
                    <measurement group_id="B12" value="45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                    <measurement group_id="B10" value="0"/>
                    <measurement group_id="B11" value="0"/>
                    <measurement group_id="B12" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="4"/>
                    <measurement group_id="B7" value="5"/>
                    <measurement group_id="B8" value="4"/>
                    <measurement group_id="B9" value="4"/>
                    <measurement group_id="B10" value="4"/>
                    <measurement group_id="B11" value="4"/>
                    <measurement group_id="B12" value="45"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                    <measurement group_id="B10" value="0"/>
                    <measurement group_id="B11" value="0"/>
                    <measurement group_id="B12" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                    <measurement group_id="B10" value="0"/>
                    <measurement group_id="B11" value="0"/>
                    <measurement group_id="B12" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                    <measurement group_id="B10" value="0"/>
                    <measurement group_id="B11" value="0"/>
                    <measurement group_id="B12" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                    <measurement group_id="B10" value="0"/>
                    <measurement group_id="B11" value="0"/>
                    <measurement group_id="B12" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                    <measurement group_id="B10" value="0"/>
                    <measurement group_id="B11" value="0"/>
                    <measurement group_id="B12" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="3"/>
                    <measurement group_id="B7" value="5"/>
                    <measurement group_id="B8" value="4"/>
                    <measurement group_id="B9" value="4"/>
                    <measurement group_id="B10" value="4"/>
                    <measurement group_id="B11" value="4"/>
                    <measurement group_id="B12" value="44"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                    <measurement group_id="B10" value="0"/>
                    <measurement group_id="B11" value="0"/>
                    <measurement group_id="B12" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                    <measurement group_id="B10" value="0"/>
                    <measurement group_id="B11" value="0"/>
                    <measurement group_id="B12" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Verapamil + R1 (T1) vs. R1)</title>
        <description>AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. Geometric mean (gMean) presented here is an adjusted gMean and standard error (SE) presented is a geometric SE (gSE).</description>
        <time_frame>Samples were taken within 0:20 hour:minutes (hh:mm) prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.</time_frame>
        <population>Pharmacokinetic (PK) parameter analysis set (PKS): All subjects in the TS providing at least 1 primary or secondary PK parameter that was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability.</population>
        <group_list>
          <group group_id="O1">
            <title>Verapamil + R1 (T1)</title>
            <description>Participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 h prior to the R1 which is administered with 280 mL of water in trial part 1.</description>
          </group>
          <group group_id="O2">
            <title>Cocktail (R1)</title>
            <description>Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Verapamil + R1 (T1) vs. R1)</title>
          <description>AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. Geometric mean (gMean) presented here is an adjusted gMean and standard error (SE) presented is a geometric SE (gSE).</description>
          <population>Pharmacokinetic (PK) parameter analysis set (PKS): All subjects in the TS providing at least 1 primary or secondary PK parameter that was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability.</population>
          <units>Nanomole*hour/litre (nmol*h/L)</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Digoxin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.71" spread="1.10"/>
                    <measurement group_id="O2" value="13.61" spread="1.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Furosemide</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="165.80" spread="1.06"/>
                    <measurement group_id="O2" value="176.85" spread="1.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Metformin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1126.22" spread="1.05"/>
                    <measurement group_id="O2" value="1357.34" spread="1.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rosuvastatin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="98.98" spread="1.11"/>
                    <measurement group_id="O2" value="87.29" spread="1.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted geometric mean (gMean) ratio</param_type>
            <param_value>100.70</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>17.9</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>88.84</ci_lower_limit>
            <ci_upper_limit>114.15</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T1 vs. R1.</estimate_desc>
            <other_analysis_desc>Digoxin, Analysis of variance (ANOVA) model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean ratio</param_type>
            <param_value>93.76</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>12.1</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>86.12</ci_lower_limit>
            <ci_upper_limit>102.06</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T1 vs. R1.</estimate_desc>
            <other_analysis_desc>Furosemide, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean Ratio</param_type>
            <param_value>82.97</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>10.7</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>76.96</ci_lower_limit>
            <ci_upper_limit>89.46</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T1 vs. R1.</estimate_desc>
            <other_analysis_desc>Metformin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean Ratio</param_type>
            <param_value>113.40</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>21.5</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>97.62</ci_lower_limit>
            <ci_upper_limit>131.72</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T1 vs. R1.</estimate_desc>
            <other_analysis_desc>Rosuvastatin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Rifampin + R1 (T2) vs. R1)</title>
        <description>AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
        <time_frame>Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.</time_frame>
        <population>PKS</population>
        <group_list>
          <group group_id="O1">
            <title>Rifampin + R1 (T2)</title>
            <description>Participants were administered a single dose of 600 mg Rifampin film-coated tablet orally with 280 mL of water together with Cocktail in trial part 1.</description>
          </group>
          <group group_id="O2">
            <title>Cocktail (R1)</title>
            <description>Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Rifampin + R1 (T2) vs. R1)</title>
          <description>AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
          <population>PKS</population>
          <units>Nanomole*hour/litre (nmol*h/L)</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Digoxin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.89" spread="1.10"/>
                    <measurement group_id="O2" value="13.61" spread="1.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Furosemide</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="211.82" spread="1.06"/>
                    <measurement group_id="O2" value="176.85" spread="1.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Metformin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1473.38" spread="1.05"/>
                    <measurement group_id="O2" value="1357.34" spread="1.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rosuvastatin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="303.81" spread="1.11"/>
                    <measurement group_id="O2" value="87.29" spread="1.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted geometric mean (gMean) ratio</param_type>
            <param_value>131.41</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>17.9</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>115.93</ci_lower_limit>
            <ci_upper_limit>148.97</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1.</estimate_desc>
            <other_analysis_desc>Digoxin, Analysis of variance (ANOVA) model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean ratio</param_type>
            <param_value>119.78</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>12.1</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>110.03</ci_lower_limit>
            <ci_upper_limit>130.39</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1.</estimate_desc>
            <other_analysis_desc>Furosemide, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean Ratio</param_type>
            <param_value>108.55</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>10.7</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>100.68</ci_lower_limit>
            <ci_upper_limit>117.03</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1.</estimate_desc>
            <other_analysis_desc>Metformin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean Ratio</param_type>
            <param_value>348.06</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>21.5</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>299.64</ci_lower_limit>
            <ci_upper_limit>404.31</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1.</estimate_desc>
            <other_analysis_desc>Rosuvastatin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Cimetidine + R1 (T3) vs. R1)</title>
        <description>AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
        <time_frame>Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.</time_frame>
        <population>PKS</population>
        <group_list>
          <group group_id="O1">
            <title>Cimetidine + R1 (T3)</title>
            <description>Participants were administered 400 mg Cimetidine 1 tablet orally at 1 h prior to cocktail and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after cocktail (Day 2). All doses of Cimetidine administered with 240 mL water and dose of Cocktail with 280 mL of water in trial part 2.</description>
          </group>
          <group group_id="O2">
            <title>Cocktail (R1)</title>
            <description>Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Cimetidine + R1 (T3) vs. R1)</title>
          <description>AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
          <population>PKS</population>
          <units>Nanomole*hour/litre (nmol*h/L)</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Digoxin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.03" spread="1.07"/>
                    <measurement group_id="O2" value="15.15" spread="1.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Furosemide</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="196.39" spread="1.05"/>
                    <measurement group_id="O2" value="194.05" spread="1.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Metformin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2006.60" spread="1.06"/>
                    <measurement group_id="O2" value="1532.41" spread="1.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rosuvastatin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="139.54" spread="1.13"/>
                    <measurement group_id="O2" value="129.90" spread="1.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted geometric mean (gMean) ratio</param_type>
            <param_value>125.61</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>13.2</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>113.99</ci_lower_limit>
            <ci_upper_limit>138.43</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T3 vs. R1.</estimate_desc>
            <other_analysis_desc>Digoxin, Analysis of variance (ANOVA) model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean ratio</param_type>
            <param_value>101.21</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>9.2</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>94.59</ci_lower_limit>
            <ci_upper_limit>108.30</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T3 vs. R1.</estimate_desc>
            <other_analysis_desc>Furosemide, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean Ratio</param_type>
            <param_value>130.94</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>13.6</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>119.82</ci_lower_limit>
            <ci_upper_limit>143.10</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T3 vs. R1.</estimate_desc>
            <other_analysis_desc>Metformin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean Ratio</param_type>
            <param_value>107.42</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>12.9</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>97.57</ci_lower_limit>
            <ci_upper_limit>118.27</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T3 vs. R1.</estimate_desc>
            <other_analysis_desc>Rosuvastatin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Probenecid + R1 (T4) vs. R1)</title>
        <description>AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
        <time_frame>Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.</time_frame>
        <population>PKS</population>
        <group_list>
          <group group_id="O1">
            <title>Probenecid + R1 (T4)</title>
            <description>Participants were administered 2 tablets of 500 mg Probenecid (2*500 mg) orally 13 h prior and again 1 h prior to the administration of R1 on day 1. All doses of Cimetidine administered with 240 mL water and dose of R1 which is administered with 280 mL of water in trial part 3.</description>
          </group>
          <group group_id="O2">
            <title>Cocktail (R1)</title>
            <description>Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Probenecid + R1 (T4) vs. R1)</title>
          <description>AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
          <population>PKS</population>
          <units>Nanomole*hour/litre (nmol*h/L)</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Digoxin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.44" spread="1.08"/>
                    <measurement group_id="O2" value="13.52" spread="1.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Furosemide</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="483.38" spread="1.08"/>
                    <measurement group_id="O2" value="177.96" spread="1.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Metformin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1331.83" spread="1.08"/>
                    <measurement group_id="O2" value="1321.20" spread="1.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rosuvastatin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="238.16" spread="1.10"/>
                    <measurement group_id="O2" value="106.69" spread="1.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted geometric mean (gMean) ratio</param_type>
            <param_value>106.78</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>15.5</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>96.51</ci_lower_limit>
            <ci_upper_limit>118.15</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1.</estimate_desc>
            <other_analysis_desc>Digoxin, Analysis of variance (ANOVA) model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean ratio</param_type>
            <param_value>271.63</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>15.9</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>246.74</ci_lower_limit>
            <ci_upper_limit>299.03</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1.</estimate_desc>
            <other_analysis_desc>Furosemide, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean Ratio</param_type>
            <param_value>100.80</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>9.6</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>94.62</ci_lower_limit>
            <ci_upper_limit>107.39</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1.</estimate_desc>
            <other_analysis_desc>Metformin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean Ratio</param_type>
            <param_value>223.24</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>13.9</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>203.79</ci_lower_limit>
            <ci_upper_limit>244.55</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1.</estimate_desc>
            <other_analysis_desc>Rosuvastatin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T1 vs. R1)</title>
        <description>Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
        <time_frame>Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.</time_frame>
        <population>PKS</population>
        <group_list>
          <group group_id="O1">
            <title>Verapamil + R1 (T1)</title>
            <description>Participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 h prior to the R1 which is administered with 280 mL of water in trial part 1.</description>
          </group>
          <group group_id="O2">
            <title>Cocktail (R1)</title>
            <description>Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T1 vs. R1)</title>
          <description>Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
          <population>PKS</population>
          <units>Nanomole/ litre (nmol/ L)</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Digoxin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.42" spread="1.09"/>
                    <measurement group_id="O2" value="1.17" spread="1.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Furosemide</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="84.32" spread="1.06"/>
                    <measurement group_id="O2" value="88.59" spread="1.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Metformin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="179.45" spread="1.04"/>
                    <measurement group_id="O2" value="223.78" spread="1.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rosuvastatin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.90" spread="1.14"/>
                    <measurement group_id="O2" value="6.84" spread="1.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted geometric mean (gMean) ratio</param_type>
            <param_value>121.64</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>27.7</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>100.43</ci_lower_limit>
            <ci_upper_limit>147.33</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T1 vs. R1.</estimate_desc>
            <other_analysis_desc>Digoxin, Analysis of variance (ANOVA) model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean ratio</param_type>
            <param_value>95.18</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>19.6</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>83.03</ci_lower_limit>
            <ci_upper_limit>109.11</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T1 vs. R1.</estimate_desc>
            <other_analysis_desc>Furosemide, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean Ratio</param_type>
            <param_value>80.19</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>13.4</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>73.01</ci_lower_limit>
            <ci_upper_limit>88.08</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T1 vs. R1.</estimate_desc>
            <other_analysis_desc>Metformin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean Ratio</param_type>
            <param_value>115.39</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>30.1</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>93.80</ci_lower_limit>
            <ci_upper_limit>141.94</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T1 vs. R1.</estimate_desc>
            <other_analysis_desc>Rosuvastatin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T2 vs. R1)</title>
        <description>Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
        <time_frame>Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.</time_frame>
        <population>PKS</population>
        <group_list>
          <group group_id="O1">
            <title>Rifampin + R1 (T2)</title>
            <description>Participants were administered a single dose of 600 mg Rifampin film-coated tablet orally with 280 mL of water together with Cocktail in trial part 1.</description>
          </group>
          <group group_id="O2">
            <title>Cocktail (R1)</title>
            <description>Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T2 vs. R1)</title>
          <description>Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
          <population>PKS</population>
          <units>Nanomole/ litre (nmol/ L)</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Digoxin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.55" spread="1.09"/>
                    <measurement group_id="O2" value="1.17" spread="1.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Furosemide</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="119.66" spread="1.06"/>
                    <measurement group_id="O2" value="88.59" spread="1.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Metformin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="251.32" spread="1.04"/>
                    <measurement group_id="O2" value="223.78" spread="1.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rosuvastatin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="77.00" spread="1.14"/>
                    <measurement group_id="O2" value="6.84" spread="1.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted geometric mean (gMean) ratio</param_type>
            <param_value>218.26</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>27.7</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>180.19</ci_lower_limit>
            <ci_upper_limit>264.36</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1.</estimate_desc>
            <other_analysis_desc>Digoxin, Analysis of variance (ANOVA) model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean ratio</param_type>
            <param_value>135.07</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>19.6</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>117.83</ci_lower_limit>
            <ci_upper_limit>154.84</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1.</estimate_desc>
            <other_analysis_desc>Furosemide, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean Ratio</param_type>
            <param_value>112.31</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>13.4</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>102.26</ci_lower_limit>
            <ci_upper_limit>123.35</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1.</estimate_desc>
            <other_analysis_desc>Metformin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean Ratio</param_type>
            <param_value>1125.10</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>30.1</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>914.63</ci_lower_limit>
            <ci_upper_limit>1384.00</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1.</estimate_desc>
            <other_analysis_desc>Rosuvastatin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T3 vs. R1)</title>
        <description>Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
        <time_frame>Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.</time_frame>
        <population>PKS</population>
        <group_list>
          <group group_id="O1">
            <title>Cimetidine + R1 (T3)</title>
            <description>Participants were administered 400 mg Cimetidine 1 tablet orally at 1 h prior to cocktail and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after cocktail (Day 2). All doses of Cimetidine administered with 240 mL water and dose of Cocktail with 280 mL of water in trial part 2.</description>
          </group>
          <group group_id="O2">
            <title>Cocktail (R1)</title>
            <description>Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T3 vs. R1)</title>
          <description>Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
          <population>PKS</population>
          <units>Nanomole/ litre (nmol/ L)</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Digoxin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.65" spread="1.07"/>
                    <measurement group_id="O2" value="1.35" spread="1.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Furosemide</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="97.69" spread="1.08"/>
                    <measurement group_id="O2" value="93.23" spread="1.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Metformin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="316.83" spread="1.07"/>
                    <measurement group_id="O2" value="258.33" spread="1.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rosuvastatin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.21" spread="1.15"/>
                    <measurement group_id="O2" value="11.30" spread="1.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted geometric mean (gMean) ratio</param_type>
            <param_value>218.26</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>27.7</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>180.19</ci_lower_limit>
            <ci_upper_limit>264.36</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T3 vs. R1.</estimate_desc>
            <other_analysis_desc>Digoxin, Analysis of variance (ANOVA) model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean ratio</param_type>
            <param_value>104.78</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>21.0</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>89.97</ci_lower_limit>
            <ci_upper_limit>122.03</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T3 vs. R1.</estimate_desc>
            <other_analysis_desc>Furosemide, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean Ratio</param_type>
            <param_value>122.65</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>20.1</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>107.68</ci_lower_limit>
            <ci_upper_limit>139.69</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1.</estimate_desc>
            <other_analysis_desc>Metformin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean Ratio</param_type>
            <param_value>116.88</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>14.4</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>105.07</ci_lower_limit>
            <ci_upper_limit>130.03</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T3 vs. R1.</estimate_desc>
            <other_analysis_desc>Rosuvastatin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T4 vs. R1)</title>
        <description>Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
        <time_frame>Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.</time_frame>
        <population>PKS</population>
        <group_list>
          <group group_id="O1">
            <title>Probenecid + R1 (T4)</title>
            <description>Participants were administered 2 tablets of 500 mg Probenecid (2*500 mg) orally 13 h prior and again 1 h prior to the administration of R1 on day 1. All doses of Cimetidine administered with 240 mL water and dose of R1 which is administered with 280 mL of water in trial part 3.</description>
          </group>
          <group group_id="O2">
            <title>Cocktail (R1)</title>
            <description>Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T4 vs. R1)</title>
          <description>Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
          <population>PKS</population>
          <units>Nanomole/ litre (nmol/ L)</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Digoxin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.13" spread="1.07"/>
                    <measurement group_id="O2" value="1.30" spread="1.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Furosemide</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="110.64" spread="1.07"/>
                    <measurement group_id="O2" value="90.00" spread="1.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Metformin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="246.78" spread="1.12"/>
                    <measurement group_id="O2" value="243.49" spread="1.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rosuvastatin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.29" spread="1.11"/>
                    <measurement group_id="O2" value="10.11" spread="1.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted geometric mean (gMean) ratio</param_type>
            <param_value>87.07</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>20.9</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>76.08</ci_lower_limit>
            <ci_upper_limit>99.64</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1.</estimate_desc>
            <other_analysis_desc>Digoxin, Analysis of variance (ANOVA) model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean ratio</param_type>
            <param_value>122.94</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>18.0</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>110.25</ci_lower_limit>
            <ci_upper_limit>137.09</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1.</estimate_desc>
            <other_analysis_desc>Furosemide, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean Ratio</param_type>
            <param_value>101.35</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>12.0</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>93.65</ci_lower_limit>
            <ci_upper_limit>109.70</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1.</estimate_desc>
            <other_analysis_desc>Metformin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean Ratio</param_type>
            <param_value>428.23</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>26.8</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>359.78</ci_lower_limit>
            <ci_upper_limit>509.70</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1.</estimate_desc>
            <other_analysis_desc>Rosuvastatin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T1 vs. R1)</title>
        <description>AUC0-∞, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 extrapolated to infinity is presented. AUC0-∞ not displayed for Digoxin analyte as precision was considered non-sufficient. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
        <time_frame>Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.</time_frame>
        <population>PKS</population>
        <group_list>
          <group group_id="O1">
            <title>Verapamil + R1 (T1)</title>
            <description>Participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 h prior to the R1 which is administered with 280 mL of water in trial part 1.</description>
          </group>
          <group group_id="O2">
            <title>Cocktail (R1)</title>
            <description>Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T1 vs. R1)</title>
          <description>AUC0-∞, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 extrapolated to infinity is presented. AUC0-∞ not displayed for Digoxin analyte as precision was considered non-sufficient. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
          <population>PKS</population>
          <units>Nanomole*hour/litre (nmol*h/L)</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Furosemide</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="176.44" spread="1.06"/>
                    <measurement group_id="O2" value="191.29" spread="1.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Metformin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1147.23" spread="1.05"/>
                    <measurement group_id="O2" value="1365.85" spread="1.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rosuvastatin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="116.80" spread="1.10"/>
                    <measurement group_id="O2" value="94.14" spread="1.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean ratio</param_type>
            <param_value>92.24</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>11.2</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>85.28</ci_lower_limit>
            <ci_upper_limit>99.76</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T1 vs. R1.</estimate_desc>
            <other_analysis_desc>Furosemide, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean Ratio</param_type>
            <param_value>83.99</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>10.0</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>78.32</ci_lower_limit>
            <ci_upper_limit>90.08</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T1 vs. R1.</estimate_desc>
            <other_analysis_desc>Metformin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean Ratio</param_type>
            <param_value>124.06</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>23.9</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>105.11</ci_lower_limit>
            <ci_upper_limit>146.43</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T1 vs. R1.</estimate_desc>
            <other_analysis_desc>Rosuvastatin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T2 vs. R1)</title>
        <description>AUC0-∞, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 extrapolated to infinity is presented. AUC0-∞ not displayed for Digoxin analyte as precision was considered non-sufficient. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
        <time_frame>Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.</time_frame>
        <population>PKS</population>
        <group_list>
          <group group_id="O1">
            <title>Rifampin + R1 (T2)</title>
            <description>Participants were administered a single dose of 600 mg Rifampin film-coated tablet orally with 280 mL of water together with Cocktail in trial part 1.</description>
          </group>
          <group group_id="O2">
            <title>Cocktail (R1)</title>
            <description>Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T2 vs. R1)</title>
          <description>AUC0-∞, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 extrapolated to infinity is presented. AUC0-∞ not displayed for Digoxin analyte as precision was considered non-sufficient. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
          <population>PKS</population>
          <units>Nanomole*hour/litre (nmol*h/L)</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Furosemide</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="215.63" spread="1.06"/>
                    <measurement group_id="O2" value="191.29" spread="1.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Metformin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1482.76" spread="1.05"/>
                    <measurement group_id="O2" value="1365.85" spread="1.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rosuvastatin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="320.72" spread="1.10"/>
                    <measurement group_id="O2" value="94.14" spread="1.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean Ratio</param_type>
            <param_value>112.73</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>11.2</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>104.23</ci_lower_limit>
            <ci_upper_limit>121.92</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1.</estimate_desc>
            <other_analysis_desc>Furosemide, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean Ratio</param_type>
            <param_value>108.56</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>10.0</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>101.22</ci_lower_limit>
            <ci_upper_limit>116.43</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1.</estimate_desc>
            <other_analysis_desc>Metformin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean Ratio</param_type>
            <param_value>340.67</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>23.9</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>288.63</ci_lower_limit>
            <ci_upper_limit>402.10</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T2 vs. R1.</estimate_desc>
            <other_analysis_desc>Rosuvastatin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T3 vs. R1)</title>
        <description>AUC0-∞, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 extrapolated to infinity is presented. AUC0-∞ not displayed for Digoxin analyte as precision was considered non-sufficient. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
        <time_frame>Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.</time_frame>
        <population>PKS</population>
        <group_list>
          <group group_id="O1">
            <title>Cimetidine + R1 (T3)</title>
            <description>Participants were administered 400 mg Cimetidine 1 tablet orally at 1 h prior to cocktail and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after cocktail (Day 2). All doses of Cimetidine administered with 240 mL water and dose of Cocktail with 280 mL of water in trial part 2.</description>
          </group>
          <group group_id="O2">
            <title>Cocktail (R1)</title>
            <description>Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T3 vs. R1)</title>
          <description>AUC0-∞, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 extrapolated to infinity is presented. AUC0-∞ not displayed for Digoxin analyte as precision was considered non-sufficient. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
          <population>PKS</population>
          <units>Nanomole*hour/litre (nmol*h/L)</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Furosemide</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="202.17" spread="1.04"/>
                    <measurement group_id="O2" value="200.61" spread="1.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Metformin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2023.33" spread="1.06"/>
                    <measurement group_id="O2" value="1540.21" spread="1.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rosuvastatin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="148.32" spread="1.13"/>
                    <measurement group_id="O2" value="139.21" spread="1.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean ratio</param_type>
            <param_value>100.78</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>10.0</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>93.59</ci_lower_limit>
            <ci_upper_limit>108.51</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T3 vs. R1.</estimate_desc>
            <other_analysis_desc>Furosemide, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean Ratio</param_type>
            <param_value>131.37</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>13.4</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>120.37</ci_lower_limit>
            <ci_upper_limit>143.37</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1.</estimate_desc>
            <other_analysis_desc>Furosemide, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean Ratio</param_type>
            <param_value>106.55</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>12.8</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>96.87</ci_lower_limit>
            <ci_upper_limit>117.19</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T3 vs. R1.</estimate_desc>
            <other_analysis_desc>Rosuvastatin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T4 vs. R1)</title>
        <description>AUC0-∞, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 extrapolated to infinity is presented. AUC0-∞ not displayed for Digoxin analyte as precision was considered non-sufficient. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
        <time_frame>Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.</time_frame>
        <population>PKS</population>
        <group_list>
          <group group_id="O1">
            <title>Probenecid + R1 (T4)</title>
            <description>Participants were administered 2 tablets of 500 mg Probenecid (2*500 mg) orally 13 h prior and again 1 h prior to the administration of R1 on day 1. All doses of Cimetidine administered with 240 mL water and dose of R1 which is administered with 280 mL of water in trial part 3.</description>
          </group>
          <group group_id="O2">
            <title>Cocktail (R1)</title>
            <description>Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T4 vs. R1)</title>
          <description>AUC0-∞, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 extrapolated to infinity is presented. AUC0-∞ not displayed for Digoxin analyte as precision was considered non-sufficient. gMean presented here is an adjusted gMean and SE presented is a gSE.</description>
          <population>PKS</population>
          <units>Nanomole*hour/litre (nmol*h/L)</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Furosemide</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="489.28" spread="1.07"/>
                    <measurement group_id="O2" value="188.11" spread="1.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Metformin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1346.62" spread="1.08"/>
                    <measurement group_id="O2" value="1330.47" spread="1.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rosuvastatin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="244.94" spread="1.10"/>
                    <measurement group_id="O2" value="113.78" spread="1.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean ratio</param_type>
            <param_value>260.11</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>14.7</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>237.96</ci_lower_limit>
            <ci_upper_limit>284.32</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1.</estimate_desc>
            <other_analysis_desc>Furosemide, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean Ratio</param_type>
            <param_value>101.21</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>9.4</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>95.15</ci_lower_limit>
            <ci_upper_limit>107.66</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1.</estimate_desc>
            <other_analysis_desc>Metformin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Adjusted gMean Ratio</param_type>
            <param_value>215.28</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>13.1</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>197.53</ci_lower_limit>
            <ci_upper_limit>234.63</ci_upper_limit>
            <estimate_desc>Standard Error of the mean is actually intra individual geometric coefficient of variation (gCV). Adjusted gMean ratio is given for T4 vs. R1.</estimate_desc>
            <other_analysis_desc>Rosuvastatin, ANOVA model on the logarithmic scale includes effects accounting for the following sources of variation: 'sequence', 'subjects within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.</time_frame>
      <desc>Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.</desc>
      <group_list>
        <group group_id="E1">
          <title>Cocktail (R1)</title>
          <description>Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3.</description>
        </group>
        <group group_id="E2">
          <title>Verapamil + R1 (T1)</title>
          <description>Participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 h prior to the R1 which is administered with 280 mL of water in trial part 1.</description>
        </group>
        <group group_id="E3">
          <title>Rifampin + R1 (T2)</title>
          <description>Participants were administered a single dose of 600 mg Rifampin film-coated tablet orally with 280 mL of water together with R1 in trial part 1.</description>
        </group>
        <group group_id="E4">
          <title>Metformin (R2)</title>
          <description>Participants were administered a single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in trial part 2.</description>
        </group>
        <group group_id="E5">
          <title>Cimetidine + R1 (T3)</title>
          <description>Participants were administered 400 mg Cimetidine 1 tablet orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2). All doses of Cimetidine administered with 240 mL water and dose of R1 which is administered with 280 mL of water in trial part 2.</description>
        </group>
        <group group_id="E6">
          <title>Cimetidine + R2 (T5)</title>
          <description>Participants were administered 400 mg Cimetidine 1 tablet orally at 1 h prior to Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after therapeutic dose of 500 mg Metformin (Day 2) in trial part 2.</description>
        </group>
        <group group_id="E7">
          <title>Furosemide (R3)</title>
          <description>Participants were administered orally a single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in trial part 3.</description>
        </group>
        <group group_id="E8">
          <title>Probenecid + R1 (T4)</title>
          <description>Participants were administered 2 tablets of 500 mg Probenecid (2*500 mg) orally 13 h prior and again 1 h prior to the administration of R1 on day 1. All doses of Cimetidine administered with 240 mL water and dose of R1 which is administered with 280 mL of water in trial part 3.</description>
        </group>
        <group group_id="E9">
          <title>Probenecid + R3 (T6)</title>
          <description>Participants were administered 2 tablets of 500 mg Probenecid (2*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in trial part 3.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 21.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="7" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="7" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="4" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="4" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="3" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Orthostatic intolerance</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Conversion disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Restlessness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Boehringer Ingelheim, Call Centre</name_or_title>
      <organization>Boehringer Ingelheim</organization>
      <phone>1-800-243-0127</phone>
      <email>clintriage.rdg@boehringer-ingelheim.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03307252
org study id: 0352-2100
secondary id: 2017-001549-29
nct id: NCT03307252
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The primary objective of this trial is to investigate the relative bioavailabilities of
      digoxin, furosemide, metformin and rosuvastatin given as a cocktail alone and as a cocktail
      together with the following drug transporter inhibitors:

      Part 1: verapamil (P-gp) and rifampin (OATP1B1/1B3) Part 2: cimetidine (OCT2/MATE) Part 3:
      probenecid (OAT1/3) The secondary objective is to investigate other potential changes in
      pharmacokinetics (e.g. in clearance, volume of distribution, etc.) of digoxin, furosemide,
      metformin and rosuvastatin given as a cocktail alone and as a cocktail together with the
      inhibitors describe above.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: None (Open Label)
measure: Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Verapamil + R1 (T1) vs. R1)
time frame: Samples were taken within 0:20 hour:minutes (hh:mm) prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.
description: AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. Geometric mean (gMean) presented here is an adjusted gMean and standard error (SE) presented is a geometric SE (gSE).
measure: Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Rifampin + R1 (T2) vs. R1)
time frame: Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.
description: AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.
measure: Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Cimetidine + R1 (T3) vs. R1)
time frame: Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.
description: AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.
measure: Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Probenecid + R1 (T4) vs. R1)
time frame: Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.
description: AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.
measure: Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T1 vs. R1)
time frame: Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.
description: Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.
measure: Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T2 vs. R1)
time frame: Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.
description: Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.
measure: Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T3 vs. R1)
time frame: Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.
description: Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.
measure: Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T4 vs. R1)
time frame: Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.
description: Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.
measure: Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T1 vs. R1)
time frame: Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.
description: AUC0-∞, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 extrapolated to infinity is presented. AUC0-∞ not displayed for Digoxin analyte as precision was considered non-sufficient. gMean presented here is an adjusted gMean and SE presented is a gSE.
measure: Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T2 vs. R1)
time frame: Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.
description: AUC0-∞, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 extrapolated to infinity is presented. AUC0-∞ not displayed for Digoxin analyte as precision was considered non-sufficient. gMean presented here is an adjusted gMean and SE presented is a gSE.
measure: Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T3 vs. R1)
time frame: Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.
description: AUC0-∞, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 extrapolated to infinity is presented. AUC0-∞ not displayed for Digoxin analyte as precision was considered non-sufficient. gMean presented here is an adjusted gMean and SE presented is a gSE.
measure: Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T4 vs. R1)
time frame: Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.
description: AUC0-∞, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 extrapolated to infinity is presented. AUC0-∞ not displayed for Digoxin analyte as precision was considered non-sufficient. gMean presented here is an adjusted gMean and SE presented is a gSE.
arm group label: Treatment Reference 1
arm group type: Experimental
arm group label: Treatment Reference 2
arm group type: Experimental
arm group label: Treatment Reference 3
arm group type: Experimental
arm group label: Treatment 1
arm group type: Experimental
arm group label: Treatment 2
arm group type: Experimental
arm group label: Treatment 3
arm group type: Experimental
arm group label: Treatment 4
arm group type: Experimental
arm group label: Treatment 5
arm group type: Experimental
arm group label: Treatment 6
arm group type: Experimental
intervention type: Drug
intervention name: Digoxin
description: Tablet
arm group label: Treatment 1
arm group label: Treatment 2
arm group label: Treatment 3
arm group label: Treatment 4
arm group label: Treatment Reference 1
intervention type: Drug
intervention name: Furosemide
description: Oral solution
arm group label: Treatment 1
arm group label: Treatment 2
arm group label: Treatment 3
arm group label: Treatment 4
arm group label: Treatment 6
arm group label: Treatment Reference 1
arm group label: Treatment Reference 3
intervention type: Drug
intervention name: Metformin
description: Oral solution
arm group label: Treatment 1
arm group label: Treatment 2
arm group label: Treatment 3
arm group label: Treatment 4
arm group label: Treatment 5
arm group label: Treatment Reference 1
arm group label: Treatment Reference 2
intervention type: Drug
intervention name: Rosuvastatin
description: Film-coated tablet
arm group label: Treatment 1
arm group label: Treatment 2
arm group label: Treatment 3
arm group label: Treatment 4
arm group label: Treatment Reference 1
intervention type: Drug
intervention name: Verapamil
description: Film-coated tablet
arm group label: Treatment 1
intervention type: Drug
intervention name: Rifampin
description: Film-coated tablet
arm group label: Treatment 2
intervention type: Drug
intervention name: Cimetidine
description: Tablet
arm group label: Treatment 3
arm group label: Treatment 5
intervention type: Drug
intervention name: Probenecid
description: Tablet
arm group label: Treatment 4
arm group label: Treatment 6
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Germany
url: http://trials.boehringer-ingelheim.com/
description: Related Info
responsible party type: Sponsor
mesh term: Metformin
mesh term: Rifampin
mesh term: Probenecid
mesh term: Digoxin
mesh term: Verapamil
mesh term: Furosemide
mesh term: Cimetidine
mesh term: Rosuvastatin Calcium
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 