<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/NCT04449536</url>
  </required_header>
  <id_info>
    <org_study_id>EudraCT: 2019-003412-32</org_study_id>
    <nct_id>NCT04449536</nct_id>
  </id_info>
  <brief_title>Cysteine-lowering Treatment With Mesna</brief_title>
  <acronym>CYLOB</acronym>
  <official_title>Cysteine-lowering Treatment With Mesna Against Obesity: Phase I Dose-finding Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Oslo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Oslo University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Oxford</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Oslo</source>
  <oversight_info>
    <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 study is to determine the efficacy of the drug Mesna®&#xD;
      (Uromitexan) in healthy participants with overweight or obesity with respect to change in&#xD;
      plasma concentrations of total cysteine, following single ascending doses of oral Mesna.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In both animal experiments and human studies, cysteine in the blood is strongly associated&#xD;
      with obesity. In rodents, changes in cysteine induced by dietary means are accompanied by&#xD;
      changes in fat mass.&#xD;
&#xD;
      In this phase I, single ascending dose study the investigators will determine the effects of&#xD;
      Mesna in healthy volunteers with overweight and obesity with focus on its effects on plasma&#xD;
      total cysteine concentrations. The aim of this dose-finding clinical trial is to determine&#xD;
      the lowest single oral Mesna dose that will lower plasma total cysteine concentrations by 30%&#xD;
      using pharmacokinetic (PK)/ pharmacodynamic (PD) modelling. The investigators will further&#xD;
      evaluate the effect of Mesna on plasma cysteine fractions and related metabolites, urinary&#xD;
      cysteine excretion, safety and adverse drug reactions, and plasma biomarkers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2, 2020</start_date>
  <completion_date type="Actual">October 21, 2021</completion_date>
  <primary_completion_date type="Actual">October 21, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in plasma total cysteine concentrations following single ascending doses of oral Mesna.</measure>
    <time_frame>Several intervals during the first 12 hours after Mensa administration, and a fasting sample on days 2 and 3</time_frame>
    <description>Nadir plasma total cysteine concentrations</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameter - maximum plasma concentration (Cmax)</measure>
    <time_frame>Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3</time_frame>
    <description>Maximum plasma Mesna concentration (Cmax) after a single oral Mesna dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameter - time to maximum plasma concentration (Tmax)</measure>
    <time_frame>Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3</time_frame>
    <description>Time to maximum plasma Mesna concentration (Tmax) after a single oral Mesna dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameter - area under the plasma concentration-time curve (AUC)</measure>
    <time_frame>Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3</time_frame>
    <description>Area under the plasma Mesna concentration-time curve (AUC)0-inf after a single oral Mesna dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameter - elimination rate constant (Kel)</measure>
    <time_frame>Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3</time_frame>
    <description>Elimination rate constant (Kel) for Mesna after a single oral Mesna dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameter - dose linearity</measure>
    <time_frame>Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3</time_frame>
    <description>Dose linearity of Mesna after a single oral Mesna dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in plasma cystine, free reduced cysteine, and protein bound cysteine</measure>
    <time_frame>Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3</time_frame>
    <description>Estimated AUCs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urine excretion of cysteine</measure>
    <time_frame>During the first 24 hours after Mesna administration</time_frame>
    <description>Cumulative and fractional excretion of total cysteine and Mesna</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety of Mesna</measure>
    <time_frame>During the first 5 days after Mesna administration</time_frame>
    <description>Occurrence/prevalence of side effects, adverse events, and serious adverse events</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Changes in plasma and urine sulfur amino acids and related metabolites</measure>
    <time_frame>Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3</time_frame>
    <description>Estimated AUCs</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in plasma biomarker concentration - glucose</measure>
    <time_frame>During the first 24 hours after Mesna administration, and a fasting sample on days 2 and 3</time_frame>
    <description>Estimated AUC</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in plasma biomarker concentration - insulin</measure>
    <time_frame>During the first 24 hours after Mesna administration, and a fasting sample on days 2 and 3</time_frame>
    <description>Estimated AUC</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in plasma biomarker concentration - lipids</measure>
    <time_frame>During the first 24 hours after Mesna administration, and a fasting sample on days 2 and 3</time_frame>
    <description>Estimated AUC</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Obesity</condition>
  <condition>Drug Effect</condition>
  <arm_group>
    <arm_group_label>Mesna</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Administration of a single oral dose of 400 mg, 800 mg, 1200 mg or 1600 mg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mesna</intervention_name>
    <description>Administration of a single oral dose, using film-coated tablets of either 400 mg or 600 mg or a combination of maximum 3 tablets up to a maximum of 1600 mg</description>
    <arm_group_label>Mesna</arm_group_label>
    <other_name>Uromitexan</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  BMI between BMI 27-40 kg/m2&#xD;
&#xD;
          -  Age between 18-55 years&#xD;
&#xD;
          -  Male&#xD;
&#xD;
          -  Healthy as determined by medical evaluation, medical history, physical examination,&#xD;
             12-lead ECG, and laboratory tests&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of chronic disease&#xD;
&#xD;
          -  Chronic drug use&#xD;
&#xD;
          -  Past or intended use of over-the-counter or prescription medication including herbal&#xD;
             medications within 14 days prior to dosing&#xD;
&#xD;
          -  Veganism&#xD;
&#xD;
          -  Strenuous physical activity ≥3 times every week&#xD;
&#xD;
          -  Smoking&#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>
  <overall_official>
    <last_name>Kjetil Retterstøl, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Oslo</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Oslo</name>
      <address>
        <city>Oslo</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Norway</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>June 15, 2020</study_first_submitted>
  <study_first_submitted_qc>June 25, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 29, 2020</study_first_posted>
  <last_update_submitted>May 18, 2022</last_update_submitted>
  <last_update_submitted_qc>May 18, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 19, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Oslo</investigator_affiliation>
    <investigator_full_name>Kathrine Vinknes</investigator_full_name>
    <investigator_title>Researcher and Project manager</investigator_title>
  </responsible_party>
  <keyword>Cysteine</keyword>
  <keyword>Phase 1</keyword>
  <keyword>Mesna</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Obesity</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mesna</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Data that support the findings of this study may be available upon reasonable request from qualified users.</ipd_description>
  </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/NCT04449536
org study id: EudraCT: 2019-003412-32
nct id: NCT04449536
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
The primary objective of this study is to determine the efficacy of the drug Mesna®
      (Uromitexan) in healthy participants with overweight or obesity with respect to change in
      plasma concentrations of total cysteine, following single ascending doses of oral Mesna.
In both animal experiments and human studies, cysteine in the blood is strongly associated
      with obesity. In rodents, changes in cysteine induced by dietary means are accompanied by
      changes in fat mass.

      In this phase I, single ascending dose study the investigators will determine the effects of
      Mesna in healthy volunteers with overweight and obesity with focus on its effects on plasma
      total cysteine concentrations. The aim of this dose-finding clinical trial is to determine
      the lowest single oral Mesna dose that will lower plasma total cysteine concentrations by 30%
      using pharmacokinetic (PK)/ pharmacodynamic (PD) modelling. The investigators will further
      evaluate the effect of Mesna on plasma cysteine fractions and related metabolites, urinary
      cysteine excretion, safety and adverse drug reactions, and plasma biomarkers.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in plasma total cysteine concentrations following single ascending doses of oral Mesna.
time frame: Several intervals during the first 12 hours after Mensa administration, and a fasting sample on days 2 and 3
description: Nadir plasma total cysteine concentrations
measure: Pharmacokinetic parameter - maximum plasma concentration (Cmax)
time frame: Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
description: Maximum plasma Mesna concentration (Cmax) after a single oral Mesna dose
measure: Pharmacokinetic parameter - time to maximum plasma concentration (Tmax)
time frame: Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
description: Time to maximum plasma Mesna concentration (Tmax) after a single oral Mesna dose
measure: Pharmacokinetic parameter - area under the plasma concentration-time curve (AUC)
time frame: Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
description: Area under the plasma Mesna concentration-time curve (AUC)0-inf after a single oral Mesna dose
measure: Pharmacokinetic parameter - elimination rate constant (Kel)
time frame: Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
description: Elimination rate constant (Kel) for Mesna after a single oral Mesna dose
measure: Pharmacokinetic parameter - dose linearity
time frame: Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
description: Dose linearity of Mesna after a single oral Mesna dose
measure: Change in plasma cystine, free reduced cysteine, and protein bound cysteine
time frame: Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
description: Estimated AUCs
measure: Urine excretion of cysteine
time frame: During the first 24 hours after Mesna administration
description: Cumulative and fractional excretion of total cysteine and Mesna
measure: Safety of Mesna
time frame: During the first 5 days after Mesna administration
description: Occurrence/prevalence of side effects, adverse events, and serious adverse events
measure: Changes in plasma and urine sulfur amino acids and related metabolites
time frame: Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
description: Estimated AUCs
measure: Changes in plasma biomarker concentration - glucose
time frame: During the first 24 hours after Mesna administration, and a fasting sample on days 2 and 3
description: Estimated AUC
measure: Changes in plasma biomarker concentration - insulin
time frame: During the first 24 hours after Mesna administration, and a fasting sample on days 2 and 3
description: Estimated AUC
measure: Changes in plasma biomarker concentration - lipids
time frame: During the first 24 hours after Mesna administration, and a fasting sample on days 2 and 3
description: Estimated AUC
arm group label: Mesna
arm group type: Experimental
description: Administration of a single oral dose of 400 mg, 800 mg, 1200 mg or 1600 mg
intervention type: Drug
intervention name: Mesna
description: Administration of a single oral dose, using film-coated tablets of either 400 mg or 600 mg or a combination of maximum 3 tablets up to a maximum of 1600 mg
arm group label: Mesna
other name: Uromitexan
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Kjetil Retterstøl, MD, PhD
role: Principal Investigator
affiliation: University of Oslo
facility: 
country: Norway
responsible party type: Principal Investigator
investigator affiliation: University of Oslo
investigator full name: Kathrine Vinknes
investigator title: Researcher and Project manager
mesh term: Obesity
mesh term: Mesna
sharing ipd: No
ipd description: Data that support the findings of this study may be available upon reasonable request from qualified users.