<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/NCT03011463</url>
  </required_header>
  <id_info>
    <org_study_id>P334</org_study_id>
    <nct_id>NCT03011463</nct_id>
  </id_info>
  <brief_title>Pharmacokinetic Interaction Between Trospium With an Inhibitor of OCT1 and of P-gp in Subjects Genotyped for OCT1</brief_title>
  <official_title>Pharmacokinetic Interaction Between Trospium Chloride After Intravenous (2 mg) and Oral Administration (30 mg) With Ranitidine (300 mg p.o.) as an Inhibitor of OCT1 and With Clarithromycin (500 mg p.o.) as an Inhibitor of P-glycoprotein in 24 Healthy Subjects Genotyped for OCT1</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dr. R. Pfleger Chemische Fabrik GmbH</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Dr. R. Pfleger Chemische Fabrik GmbH</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is:&#xD;
&#xD;
        -  to determine absolute bioavailability, input rates, distribution volume, renal and&#xD;
           intestinal excretion of trospium in subjects with wild-type of SLC22A1 rs72552763 and&#xD;
           rs12208357 and in subjects with homozygous variant alleles of SLC22A1 rs72552763 or&#xD;
           rs12208357&#xD;
&#xD;
        -  to determine absolute bioavailability, input rates, distribution volume and renal and&#xD;
           intestinal excretion of trospium in subjects with wild-type alleles of SLC22A1&#xD;
           rs72552763 and rs12208357 after co-medication of 300 mg of the OCT1- inhibitor&#xD;
           ranitidine&#xD;
&#xD;
        -  to determine absolute bioavailability, input rates, distribution volume and renal and&#xD;
           intestinal excretion of trospium in subjects with wild-type alleles of SLC22A1&#xD;
           rs72552763 and rs12208357 after co-medication of 500 mg of the P-glycoprotein- inhibitor&#xD;
           clarithromycin&#xD;
&#xD;
        -  to determine absolute bioavailability, input rates, distribution volume and renal and&#xD;
           intestinal excretion of trospium in subjects with homozygous variant alleles of SLC22A1&#xD;
           rs72552763 or rs12208357 after co-medication of 500 mg of the P-glycoprotein- inhibitor&#xD;
           clarithromycin.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2016</start_date>
  <completion_date type="Actual">March 2017</completion_date>
  <primary_completion_date type="Actual">March 2017</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>absolute bioavailability</measure>
    <time_frame>up to 36 h after drug administration</time_frame>
    <description>ratio oral over intravenous area under the concentration time curve normalized by given dose</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>input rates</measure>
    <time_frame>up to 36 h after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>volume of distribution</measure>
    <time_frame>up to 36 h after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>renal excretion</measure>
    <time_frame>up to 36 h after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>intestinal excretion</measure>
    <time_frame>up to 36 h after drug administration</time_frame>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Pharmacokinetics</condition>
  <condition>Inhibition Enzyme</condition>
  <condition>Drug Interaction Potentiation</condition>
  <arm_group>
    <arm_group_label>trospium intravenous</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intravenous infusion of 2 mg trospium chloride in 20 ml saline within 60 min and 240 ml tap water p.o.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>trospium oral</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Oral administration of 30 mg trospium chloride with 240 ml tap water</description>
  </arm_group>
  <arm_group>
    <arm_group_label>trospium intravenous with ranitidine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intravenous infusion of 2 mg trospium chloride in 20 ml saline within 60 min and oral administration of 300 mg ranitidine with 240 ml tap water</description>
  </arm_group>
  <arm_group>
    <arm_group_label>trospium intravenous with clarithromycin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intravenous infusion of 2 mg trospium chloride in 20 ml saline within 60 min and oral administration of 500 mg clarithromycin with 240 ml tap water</description>
  </arm_group>
  <arm_group>
    <arm_group_label>trospium oral with ranitidine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Oral administration of 30 mg trospium chloride together with 300 mg ranitidine with 240 ml tap water</description>
  </arm_group>
  <arm_group>
    <arm_group_label>trospium oral with clarithromycin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Oral administration of 30 mg trospium chloride together with 500 mg clarithromycin with 240 ml tap water</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>intravenous infusion of 2 mg trospium chloride</intervention_name>
    <description>intravenous infusion of 2 mg trospium chloride in 20 ml saline within 60 min and 240 ml tap water p.o</description>
    <arm_group_label>trospium intravenous</arm_group_label>
    <arm_group_label>trospium intravenous with clarithromycin</arm_group_label>
    <arm_group_label>trospium intravenous with ranitidine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>oral administration of 30 mg trospium chloride</intervention_name>
    <description>oral administration of 30 mg trospium chloride with 240 ml tap water</description>
    <arm_group_label>trospium oral</arm_group_label>
    <arm_group_label>trospium oral with clarithromycin</arm_group_label>
    <arm_group_label>trospium oral with ranitidine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>oral administration of 300 mg ranitidine</intervention_name>
    <description>oral administration of 300 mg ranitidine with 240 ml tap water</description>
    <arm_group_label>trospium intravenous with ranitidine</arm_group_label>
    <arm_group_label>trospium oral with ranitidine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>oral administration of 500 mg clarithromycin</intervention_name>
    <description>oral administration of 500 mg clarithromycin with 240 ml tap water</description>
    <arm_group_label>trospium intravenous with clarithromycin</arm_group_label>
    <arm_group_label>trospium oral with clarithromycin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ethnic origin: Caucasian&#xD;
&#xD;
          -  genotypes of OCT1: wild-type and homozygous variant alleles of SLC22A1 rs72552763 or&#xD;
             rs12208357.&#xD;
&#xD;
          -  body mass index: ≥ 18.5 kg/m² and ≤ 30 kg/m²&#xD;
&#xD;
          -  good health as evidenced by the results of the clinical examination, ECG, and the&#xD;
             laboratory check-up, which are judged by the clinical investigator not to differ in a&#xD;
             clinical relevant way from the normal state (blood pressure between 110/70 and 140/90&#xD;
             for males and between 100/60 and 140/90 for females, heart rate over 50 bpm up to 90&#xD;
             bpm, laboratory values within the reference ranges as given actually by the laboratory&#xD;
             and stored in the TMF)&#xD;
&#xD;
          -  written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  hepatic and renal diseases and/or pathological findings, which might interfere with&#xD;
             pharmacokinetics and pharmacodynamics of the study medication (e.g. hepatic or renal&#xD;
             dysfunction, obstruction of the urine flow with urinary retention by subvesical&#xD;
             obstruction like benign prostatic hyperplasia, infections or tumors of the urinary&#xD;
             tract)&#xD;
&#xD;
          -  organic causes for polydipsia and pollakiuria&#xD;
&#xD;
          -  existing cardiac or hematological diseases and/or pathological findings, which might&#xD;
             interfere with the drug's safety, tolerability and/or pharmacokinetics (e.g.&#xD;
             tachycardia, tachyarrhythmia, bradycardia, heart failure, coronary heart disease,&#xD;
             disturbance of the stimulus conduction)&#xD;
&#xD;
          -  pneumonia&#xD;
&#xD;
          -  pharyngitis&#xD;
&#xD;
          -  acute phorphyria&#xD;
&#xD;
          -  hyperthyroidism&#xD;
&#xD;
          -  galactose-intolerance, lactase deficiency or glucose-galactose malabsorption&#xD;
&#xD;
          -  electrolyte disturbance&#xD;
&#xD;
          -  gastrointestinal diseases and/or pathological findings (e.g. hiatus hernia with&#xD;
             gastroesophageal reflux, stenosis, ulcera, severe chronic inflammatory bowel disease&#xD;
             like ulcerative colitis or Crohn's disease, toxic megacolon), which might interfere&#xD;
             with pharmacokinetics and pharmacodynamics of the study medication)&#xD;
&#xD;
          -  autonomic neuropathy&#xD;
&#xD;
          -  myasthenia gravis&#xD;
&#xD;
          -  narrow-angle glaucoma&#xD;
&#xD;
          -  drug or alcohol dependence&#xD;
&#xD;
          -  positive drug or alcohol screening&#xD;
&#xD;
          -  smokers of 10 or more cigarettes per day&#xD;
&#xD;
          -  positive results in HIV, HBV and HCV screenings&#xD;
&#xD;
          -  subjects who are on a diet which could affect the pharmacokinetics of the drugs (e. g.&#xD;
             vegans, vegetarians)&#xD;
&#xD;
          -  heavy tea or coffee drinkers (more than 1L per day)&#xD;
&#xD;
          -  lactation, pregnancy test positive or not performed or women of child-bearing age&#xD;
             without safe contraception as stated in the Note for Guidance on Non-clinical Safety&#xD;
             Studies for the Conduct of Human Clinical Trials for Pharmaceutical (CPMP/ICH/286/95&#xD;
             modifications: implants, injectables, combined oral contraceptives, IUDs, sexual&#xD;
             abstinence or vasectomised partner and barrier-methods only in combination with one of&#xD;
             the aforementioned)&#xD;
&#xD;
          -  subjects suspected or known not to follow instructions of the clinical investigators&#xD;
&#xD;
          -  subjects who are unable to understand the written and verbal instructions, in&#xD;
             particular regarding the risks and inconveniences they will be exposed to as a result&#xD;
             of their participation in the study&#xD;
&#xD;
          -  subjects liable to orthostatic dysregulation, fainting, or blackouts&#xD;
&#xD;
          -  participation in a clinical trial during the last 3 months prior to the start of the&#xD;
             study&#xD;
&#xD;
          -  less than 14 days after last acute disease&#xD;
&#xD;
          -  less than 3 months after last blood donation&#xD;
&#xD;
          -  any medication within 4 weeks prior to the intended first administration of the study&#xD;
             medication which might influence functions of the gastrointestinal tract (e.g.&#xD;
             laxatives, metoclopramide, loperamide, antacids, H2-receptor antagonists, proton pump&#xD;
             inhibitors, anticholinergics)&#xD;
&#xD;
          -  any other medication within two weeks prior to the first administration of the study&#xD;
             medication, but at least 10-time the half-live of the respective drug (except oral&#xD;
             contraceptives)&#xD;
&#xD;
          -  intake of grapefruit or orange containing food or beverages within 14 days prior to&#xD;
             administration of the study medication&#xD;
&#xD;
          -  intake of poppy seed containing food or beverages within 14 days prior to&#xD;
             administration of the study medication&#xD;
&#xD;
          -  known allergic reactions to the active ingredients used, other H2-receptor&#xD;
             antagonists, macrolide antibiotics or to constituents of the study medication&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <verification_date>April 2017</verification_date>
  <study_first_submitted>January 2, 2017</study_first_submitted>
  <study_first_submitted_qc>January 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 5, 2017</study_first_posted>
  <last_update_submitted>April 7, 2017</last_update_submitted>
  <last_update_submitted_qc>April 7, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">April 10, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Medicine Greifswald</investigator_affiliation>
    <investigator_full_name>Tarek Roustom</investigator_full_name>
    <investigator_title>top doctor, clinical trial center</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Clarithromycin</mesh_term>
    <mesh_term>Ranitidine</mesh_term>
    <mesh_term>Ranitidine bismuth citrate</mesh_term>
    <mesh_term>Trospium chloride</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03011463
org study id: P334
nct id: NCT03011463
lead sponsor: 
has dmc: No
The purpose of the study is:

        -  to determine absolute bioavailability, input rates, distribution volume, renal and
           intestinal excretion of trospium in subjects with wild-type of SLC22A1 rs72552763 and
           rs12208357 and in subjects with homozygous variant alleles of SLC22A1 rs72552763 or
           rs12208357

        -  to determine absolute bioavailability, input rates, distribution volume and renal and
           intestinal excretion of trospium in subjects with wild-type alleles of SLC22A1
           rs72552763 and rs12208357 after co-medication of 300 mg of the OCT1- inhibitor
           ranitidine

        -  to determine absolute bioavailability, input rates, distribution volume and renal and
           intestinal excretion of trospium in subjects with wild-type alleles of SLC22A1
           rs72552763 and rs12208357 after co-medication of 500 mg of the P-glycoprotein- inhibitor
           clarithromycin

        -  to determine absolute bioavailability, input rates, distribution volume and renal and
           intestinal excretion of trospium in subjects with homozygous variant alleles of SLC22A1
           rs72552763 or rs12208357 after co-medication of 500 mg of the P-glycoprotein- inhibitor
           clarithromycin.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: absolute bioavailability
time frame: up to 36 h after drug administration
description: ratio oral over intravenous area under the concentration time curve normalized by given dose
measure: input rates
time frame: up to 36 h after drug administration
measure: volume of distribution
time frame: up to 36 h after drug administration
measure: renal excretion
time frame: up to 36 h after drug administration
measure: intestinal excretion
time frame: up to 36 h after drug administration
arm group label: trospium intravenous
arm group type: Active Comparator
description: Intravenous infusion of 2 mg trospium chloride in 20 ml saline within 60 min and 240 ml tap water p.o.
arm group label: trospium oral
arm group type: Active Comparator
description: Oral administration of 30 mg trospium chloride with 240 ml tap water
arm group label: trospium intravenous with ranitidine
arm group type: Active Comparator
description: Intravenous infusion of 2 mg trospium chloride in 20 ml saline within 60 min and oral administration of 300 mg ranitidine with 240 ml tap water
arm group label: trospium intravenous with clarithromycin
arm group type: Active Comparator
description: Intravenous infusion of 2 mg trospium chloride in 20 ml saline within 60 min and oral administration of 500 mg clarithromycin with 240 ml tap water
arm group label: trospium oral with ranitidine
arm group type: Active Comparator
description: Oral administration of 30 mg trospium chloride together with 300 mg ranitidine with 240 ml tap water
arm group label: trospium oral with clarithromycin
arm group type: Active Comparator
description: Oral administration of 30 mg trospium chloride together with 500 mg clarithromycin with 240 ml tap water
intervention type: Drug
intervention name: intravenous infusion of 2 mg trospium chloride
description: intravenous infusion of 2 mg trospium chloride in 20 ml saline within 60 min and 240 ml tap water p.o
arm group label: trospium intravenous
arm group label: trospium intravenous with clarithromycin
arm group label: trospium intravenous with ranitidine
intervention type: Drug
intervention name: oral administration of 30 mg trospium chloride
description: oral administration of 30 mg trospium chloride with 240 ml tap water
arm group label: trospium oral
arm group label: trospium oral with clarithromycin
arm group label: trospium oral with ranitidine
intervention type: Drug
intervention name: oral administration of 300 mg ranitidine
description: oral administration of 300 mg ranitidine with 240 ml tap water
arm group label: trospium intravenous with ranitidine
arm group label: trospium oral with ranitidine
intervention type: Drug
intervention name: oral administration of 500 mg clarithromycin
description: oral administration of 500 mg clarithromycin with 240 ml tap water
arm group label: trospium intravenous with clarithromycin
arm group label: trospium oral with clarithromycin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
responsible party type: Principal Investigator
investigator affiliation: University Medicine Greifswald
investigator full name: Tarek Roustom
investigator title: top doctor, clinical trial center
mesh term: Clarithromycin
mesh term: Ranitidine
mesh term: Ranitidine bismuth citrate
mesh term: Trospium chloride
sharing ipd: No