<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/NCT03012763</url>
  </required_header>
  <id_info>
    <org_study_id>GIT-Physiol_2016</org_study_id>
    <nct_id>NCT03012763</nct_id>
  </id_info>
  <brief_title>Oral Pharmacokinetics of Sulfasalazine, Paracetamol, Fexofenadine and Valsartan Using Different Administration Mediums</brief_title>
  <official_title>Pharmacokinetics of Sulfasalazine, Paracetamol, Fexofenadine and Valsartan After Oral Administration Using 240 ml Non-caloric Water, a Carbohydrate Enriched Drink and Grapefruit Juice in Correlation to the Intestinal Availability of Water as Quantified by MRI-based Volumetry in 9 Healthy Male and Female Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Medicine Greifswald</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Medicine Greifswald</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine pharmacokinetics of the probe-drugs sulfasalazine,&#xD;
      given in 240 ml non-caloric water and paracetamol, fexofenadine and valsartan after oral&#xD;
      administration, given in 240 ml non-caloric water, in 240 ml caloric drink or in 240 ml&#xD;
      grapefruit juice prior to ingestion and to visualize the localization and to measure the&#xD;
      filling volume of stomach, small intestine as well as ascending, transverse and descending&#xD;
      colon by T2-weighted magnetic resonance imaging after oral administration of 240 ml water&#xD;
      (non-caloric water), after administration of 240 ml caloric drink and after administration of&#xD;
      240 ml grapefruit juice.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>April 2016</start_date>
  <primary_completion_date type="Actual">January 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>area under the concentration time curve (AUC)</measure>
    <time_frame>up to 51 h after drug administration</time_frame>
    <description>Computed with the measured concentration of Paracetamol, Fexofenadine and Valsartan in blood samples.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>area under the curve of small bowel water volume</measure>
    <time_frame>up to 6.75 h after drug administration</time_frame>
    <description>Dynamic enhanced magnetic resonance examination gradient-echo T2-weighted HASTE images (TR 1300 ms, TR 321 ms, flip-angle 160°) will be acquired on a 1.5 Tesla MRI. A tube filled with 20 ml water will be fitted on the abdomen of the volunteers in order to have an internal reference for imaging. The obtained MRI files will be investigated with common radiological software (OsiriX, Voxar 3D, Fiji, 3D slicer). From the DICOM files there will obtained: Gastrointestinal volumes and their kinetics for stomach, small bowel, colon segments and gallbladder.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>gastric emptying rate</measure>
    <time_frame>up to 6.75 h after drug administration</time_frame>
    <description>Dynamic enhanced magnetic resonance examination gradient-echo T2-weighted HASTE images (TR 1300 ms, TR 321 ms, flip-angle 160°) will be acquired on a 1.5 Tesla MRI. A tube filled with 20 ml water will be fitted on the abdomen of the volunteers in order to have an internal reference for imaging. The obtained MRI files will be investigated with common radiological software (OsiriX, Voxar 3D, Fiji, 3D slicer). From the DICOM files there will obtained: Gastrointestinal volumes and their kinetics for stomach, small bowel, colon segments and gallbladder. Gastric emptying rate will be estimated as the half life of water volumen in the stomach.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>lag-Time of sulfapyridine (orocecal transit times)</measure>
    <time_frame>up to 51 h after drug administration</time_frame>
    <description>Estimated as the first significant concentration (&gt;50 or 100 ng/ml) of sulfapyridine in blood samples after administration of Sulfasalazine.</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Pharmacokinetics</condition>
  <condition>Magnetic Resonance Imaging</condition>
  <condition>Administration, Oral</condition>
  <arm_group>
    <arm_group_label>non-caloric water</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>50 mg sulfasalazine given in 240 ml table water after 6 h fasting and 250 mg paracetamol, 120 mg fexofenadine and 40 mg valsartan given in 240 ml non-caloric water 3 h thereafter</description>
  </arm_group>
  <arm_group>
    <arm_group_label>caloric drink</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>50 mg sulfasalazine given in 240 ml table water after 6 h fasting and 250 mg paracetamol, 120 mg fexofenadine and 40 mg valsartan given in 240 ml caloric drink 3 h thereafter</description>
  </arm_group>
  <arm_group>
    <arm_group_label>grapefruit juice</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>50 mg sulfasalazine given in 240 ml table water after 6 h fasting and 250 mg paracetamol, 120 mg fexofenadine and 40 mg valsartan given in 240 ml grapefruit juice 3 h thereafter</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paracetamol</intervention_name>
    <description>Oral administration of 250 mg paracetamol</description>
    <arm_group_label>caloric drink</arm_group_label>
    <arm_group_label>grapefruit juice</arm_group_label>
    <arm_group_label>non-caloric water</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sulfasalazine</intervention_name>
    <description>Oral administration of 50 mg sulfasalazine</description>
    <arm_group_label>caloric drink</arm_group_label>
    <arm_group_label>grapefruit juice</arm_group_label>
    <arm_group_label>non-caloric water</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fexofenadine</intervention_name>
    <description>Oral administration of 120 mg fexofenadine</description>
    <arm_group_label>caloric drink</arm_group_label>
    <arm_group_label>grapefruit juice</arm_group_label>
    <arm_group_label>non-caloric water</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Valsartan</intervention_name>
    <description>Oral administration of 40 mg valsartan</description>
    <arm_group_label>caloric drink</arm_group_label>
    <arm_group_label>grapefruit juice</arm_group_label>
    <arm_group_label>non-caloric water</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>non-caloric water</intervention_name>
    <description>Oral administration of 240 ml non-caloric water</description>
    <arm_group_label>non-caloric water</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>caloric drink</intervention_name>
    <description>Oral administration of 240 ml caloric drink</description>
    <arm_group_label>caloric drink</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>grapefruit juice</intervention_name>
    <description>Oral administration of 240 ml grapefruit juice</description>
    <arm_group_label>grapefruit juice</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ethnic origin: Caucasian&#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&#xD;
&#xD;
          -  written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  weight less than 45 kg&#xD;
&#xD;
          -  claustrophobia&#xD;
&#xD;
          -  tinnitus&#xD;
&#xD;
          -  cardiac pacemakers, metallic, plastic or silicone implants, dental retainer or&#xD;
             metal-containing tattoos and piercings, Permanent Make-Ups, intrauterine devices&#xD;
&#xD;
          -  known allergic reactions/ hypersensitivity to the active ingredients used or to&#xD;
             constituents of the study medication (e.g. lactose, lecithin, sulfonamides,&#xD;
             salicylates)&#xD;
&#xD;
          -  bronchial asthma (all stages) and other known allergic diseases&#xD;
&#xD;
          -  existing cardiac, haematopoietic or hematological diseases and/or pathological&#xD;
             findings, which might interfere with the drug's safety, tolerability and/or&#xD;
             pharmacokinetics or the requirements for the magnetic resonance tomography&#xD;
&#xD;
          -  known hyperkalemia, hyponatremia or hypovolemia or medications that may cause these&#xD;
             conditions.&#xD;
&#xD;
          -  Hepatic, renal or metabolic diseases and/or pathological findings, which might&#xD;
             interfere with pharmacokinetics and pharmacodynamics of the study medication (e.g.&#xD;
             liver failure, kidney failure, acute intermittent porphyria).&#xD;
&#xD;
          -  gastrointestinal diseases and/or pathological findings, which might interfere with&#xD;
             gastrointestinal motility and emptying processes and interfering with pharmacokinetics&#xD;
             and pharmacodynamics of the study medication (e.g. ileus)&#xD;
&#xD;
          -  Erythema exsudativum multiforme.&#xD;
&#xD;
          -  Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency).&#xD;
&#xD;
          -  Acute, chronic or recurrent infections.&#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, hepatitis B virus and hepatitis C virus screenings&#xD;
&#xD;
          -  subjects who are on a diet which could affect gastrointestinal motility or the&#xD;
             pharmacokinetics of the drug (vegetarian, vegan)&#xD;
&#xD;
          -  eating disorders e.g. anorexia, bulimia&#xD;
&#xD;
          -  heavy tea or coffee drinkers (more than 1l per day)&#xD;
&#xD;
          -  lactation and/or pregnancy test positive or not performed&#xD;
&#xD;
          -  subjects suspected or known not to follow instructions&#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 planned start&#xD;
             of the study less than 3 months after last blood donation&#xD;
&#xD;
          -  therapy with transdermal patches&#xD;
&#xD;
          -  any systemically available medication within 2 weeks prior to the intended first&#xD;
             administration unless because of the terminal elimination half-life complete&#xD;
             elimination from the body can be assumed for the drug and/or its primary metabolites&#xD;
             (except oral contraceptives)&#xD;
&#xD;
          -  intake of grapefruit or poppy seeds containing products within 14 days prior to the&#xD;
             start of the study&#xD;
&#xD;
          -  Females who don't fulfil the criteria for contraception as listed in section 7.5.1 of&#xD;
             this protocol&#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>January 2017</verification_date>
  <study_first_submitted>January 5, 2017</study_first_submitted>
  <study_first_submitted_qc>January 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 6, 2017</study_first_posted>
  <last_update_submitted>January 5, 2017</last_update_submitted>
  <last_update_submitted_qc>January 5, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 6, 2017</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>Acetaminophen</mesh_term>
    <mesh_term>Fexofenadine</mesh_term>
    <mesh_term>Sulfasalazine</mesh_term>
    <mesh_term>Valsartan</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/NCT03012763
org study id: GIT-Physiol_2016
nct id: NCT03012763
lead sponsor: 
has dmc: No
The purpose of this study is to determine pharmacokinetics of the probe-drugs sulfasalazine,
      given in 240 ml non-caloric water and paracetamol, fexofenadine and valsartan after oral
      administration, given in 240 ml non-caloric water, in 240 ml caloric drink or in 240 ml
      grapefruit juice prior to ingestion and to visualize the localization and to measure the
      filling volume of stomach, small intestine as well as ascending, transverse and descending
      colon by T2-weighted magnetic resonance imaging after oral administration of 240 ml water
      (non-caloric water), after administration of 240 ml caloric drink and after administration of
      240 ml grapefruit juice.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: area under the concentration time curve (AUC)
time frame: up to 51 h after drug administration
description: Computed with the measured concentration of Paracetamol, Fexofenadine and Valsartan in blood samples.
measure: area under the curve of small bowel water volume
time frame: up to 6.75 h after drug administration
description: Dynamic enhanced magnetic resonance examination gradient-echo T2-weighted HASTE images (TR 1300 ms, TR 321 ms, flip-angle 160°) will be acquired on a 1.5 Tesla MRI. A tube filled with 20 ml water will be fitted on the abdomen of the volunteers in order to have an internal reference for imaging. The obtained MRI files will be investigated with common radiological software (OsiriX, Voxar 3D, Fiji, 3D slicer). From the DICOM files there will obtained: Gastrointestinal volumes and their kinetics for stomach, small bowel, colon segments and gallbladder.
measure: gastric emptying rate
time frame: up to 6.75 h after drug administration
description: Dynamic enhanced magnetic resonance examination gradient-echo T2-weighted HASTE images (TR 1300 ms, TR 321 ms, flip-angle 160°) will be acquired on a 1.5 Tesla MRI. A tube filled with 20 ml water will be fitted on the abdomen of the volunteers in order to have an internal reference for imaging. The obtained MRI files will be investigated with common radiological software (OsiriX, Voxar 3D, Fiji, 3D slicer). From the DICOM files there will obtained: Gastrointestinal volumes and their kinetics for stomach, small bowel, colon segments and gallbladder. Gastric emptying rate will be estimated as the half life of water volumen in the stomach.
measure: lag-Time of sulfapyridine (orocecal transit times)
time frame: up to 51 h after drug administration
description: Estimated as the first significant concentration (>50 or 100 ng/ml) of sulfapyridine in blood samples after administration of Sulfasalazine.
arm group label: non-caloric water
arm group type: Placebo Comparator
description: 50 mg sulfasalazine given in 240 ml table water after 6 h fasting and 250 mg paracetamol, 120 mg fexofenadine and 40 mg valsartan given in 240 ml non-caloric water 3 h thereafter
arm group label: caloric drink
arm group type: Active Comparator
description: 50 mg sulfasalazine given in 240 ml table water after 6 h fasting and 250 mg paracetamol, 120 mg fexofenadine and 40 mg valsartan given in 240 ml caloric drink 3 h thereafter
arm group label: grapefruit juice
arm group type: Active Comparator
description: 50 mg sulfasalazine given in 240 ml table water after 6 h fasting and 250 mg paracetamol, 120 mg fexofenadine and 40 mg valsartan given in 240 ml grapefruit juice 3 h thereafter
intervention type: Drug
intervention name: Paracetamol
description: Oral administration of 250 mg paracetamol
arm group label: caloric drink
arm group label: grapefruit juice
arm group label: non-caloric water
intervention type: Drug
intervention name: Sulfasalazine
description: Oral administration of 50 mg sulfasalazine
arm group label: caloric drink
arm group label: grapefruit juice
arm group label: non-caloric water
intervention type: Drug
intervention name: Fexofenadine
description: Oral administration of 120 mg fexofenadine
arm group label: caloric drink
arm group label: grapefruit juice
arm group label: non-caloric water
intervention type: Drug
intervention name: Valsartan
description: Oral administration of 40 mg valsartan
arm group label: caloric drink
arm group label: grapefruit juice
arm group label: non-caloric water
intervention type: Device
intervention name: non-caloric water
description: Oral administration of 240 ml non-caloric water
arm group label: non-caloric water
intervention type: Device
intervention name: caloric drink
description: Oral administration of 240 ml caloric drink
arm group label: caloric drink
intervention type: Device
intervention name: grapefruit juice
description: Oral administration of 240 ml grapefruit juice
arm group label: grapefruit juice
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
responsible party type: Sponsor
mesh term: Acetaminophen
mesh term: Fexofenadine
mesh term: Sulfasalazine
mesh term: Valsartan
sharing ipd: No