<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/NCT02259751</url>
  </required_header>
  <id_info>
    <org_study_id>1207.4</org_study_id>
    <nct_id>NCT02259751</nct_id>
  </id_info>
  <brief_title>Study to Determine Pharmacodynamic Effects and Pharmacokinetics of KUC 7483 CL in Patients With Spinal Cord Injury and Neurogenic Detrusor Overactivity</brief_title>
  <official_title>A Phase I, Randomised, Double-blind, Placebo-controlled Study to Determine Pharmacodynamic Effects and Pharmacokinetics of a Single Oral Dose of 320 mg KUC 7483 CL in Patients With Spinal Cord Injury and Neurogenic Detrusor Overactivity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      Study to investigate pharmacodynamic effects and pharmacokinetics of KUC 7483&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>February 2004</start_date>
  <primary_completion_date type="Actual">February 2005</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in &quot;volume at first contraction&quot;</measure>
    <time_frame>2 hours post dosing</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in &quot;volume at first contraction&quot;</measure>
    <time_frame>6 hours post dosing</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Detrusor pressure at first contraction</measure>
    <time_frame>2 and 6 hours post dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Maximum amplitude of involuntary detrusor contraction</measure>
    <time_frame>2 and 6 hours post dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Volume at first incontinence episode</measure>
    <time_frame>2 and 6 hours post dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in compliance</measure>
    <time_frame>2 and 6 hours post dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Maximum cystometric capacity</measure>
    <time_frame>2 and 6 hours post dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Detrusor pressure at maximum flow induced by triggering</measure>
    <time_frame>2 and 6 hours post dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Post-triggering residual urinary volume</measure>
    <time_frame>2 and 6 hours post dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-∞ (area under the concentration time curve of KUC 7322 ZW in plasma over the time interval from 0 extrapolated to infinity)</measure>
    <time_frame>up to 24 hours post dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax (maximum concentration of KUC 7322 ZW in plasma)</measure>
    <time_frame>up to 24 hours post dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-tz (area under the concentration-time curve of KUC 7322 ZW in plasma over the time interval from 0 to the time of the last quantifiable data point)</measure>
    <time_frame>up to 24 hours post dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-24 (Area under the concentration time curve of KUC 7322 ZW in plasma over the time interval 0 to 24 hours)</measure>
    <time_frame>up to 24 hours post dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax (time from dosing to the maximum concentration of KUC 7322 ZW in plasma)</measure>
    <time_frame>up to 24 hours post dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>λz (terminal rate constant of KUC 7322 ZW in plasma)</measure>
    <time_frame>up to 24 hours post dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2 (terminal half-life of KUC 7322 ZW in plasma)</measure>
    <time_frame>up to 24 hours post dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRTpo (mean residence time of KUC 7322 ZW in the body after po administration)</measure>
    <time_frame>up to 24 hours post dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL/F (apparent clearance of KUC 7322 ZW in the plasma after extravascular administration)</measure>
    <time_frame>up to 24 hours post dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)</measure>
    <time_frame>up to 24 hours post dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aet1-t2 (amount of KUC 7322 ZW that is eliminated in urine from the time interval t1 to t2)</measure>
    <time_frame>up to 24 hours post dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fet1-t2 (fraction of administered drug excreted unchanged in urine from time point t1 to t2)</measure>
    <time_frame>up to 24 hours post dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CLR,t1-t2 (renal clearance of KUC 7322 ZW in plasma from the time point t1 until the time point t2)</measure>
    <time_frame>up to 24 hours post dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>up to 26 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically significant changes in vital signs</measure>
    <time_frame>up to 24 hours post dosing</time_frame>
    <description>Blood Pressure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of tolerability by investigator on a 4-point scale</measure>
    <time_frame>10 days post dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of tolerability by patient on a 4-point scale</measure>
    <time_frame>10 days post dosing</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Spinal Cord Injuries</condition>
  <arm_group>
    <arm_group_label>KUC 7483 CL</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>KUC 7483 CL</intervention_name>
    <arm_group_label>KUC 7483 CL</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male patients with acquired suprasacral spinal cord injury practicing intermittent&#xD;
             catheterization under stable condition as determined by the investigator&#xD;
&#xD;
          2. Recovery from spinal shock in posttraumatic patients&#xD;
&#xD;
          3. Aged 18 - 70 years&#xD;
&#xD;
          4. BMI range ≥ 18.5 and &lt; 29.9 kg/m2&#xD;
&#xD;
          5. Documented neurogenic detrusor overactivity as shown by urodynamics within the last 12&#xD;
             months prior to study start and confirmation by the baseline urodynamics (day 2).&#xD;
             Detrusor overactivity is defined as a non-volitional increase in detrusor pressure of&#xD;
             &gt; 6 cm H2O. Detrusor sphincter dyssynergia may be facultative&#xD;
&#xD;
          6. Written informed consent consistent with International committee on harmonization&#xD;
             (ICH)/ Good Clinical Practice (GCP) and local legislation given prior to any study&#xD;
             procedures&#xD;
&#xD;
          7. Ability and willingness to comply with study treatment regimen and to attend study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. A total daily volume of urine &gt; 3000 ml as verified in the micturition diary before&#xD;
             randomization&#xD;
&#xD;
          2. Treatment with drugs with known anticholinergic effect on the detrusor and/or&#xD;
             alpha-blockers, 7 days prior to inclusion visit 2&#xD;
&#xD;
          3. Treatment with botulinus toxin, capsaicin or resiniferatoxin in the last 6 months&#xD;
             prior to the study&#xD;
&#xD;
          4. Unstable dosage of any drug or the expectation of initiation of such a treatment&#xD;
             during the trial&#xD;
&#xD;
          5. Use of agonists or antagonists at beta-adrenoceptors (The following drugs may&#xD;
             nevertheless be used since they do not act upon beta-3 adrenoceptors in therapeutic&#xD;
             doses: atenolol, bisoprolol, carvedilol, metoprolol, propranolol, salbutamol and&#xD;
             salmeterol)&#xD;
&#xD;
          6. Neurological diseases other than suprasacral spinal cord injury, affecting urinary&#xD;
             bladder function&#xD;
&#xD;
          7. Significant stress incontinence as determined by the investigator&#xD;
&#xD;
          8. Non-functional bladder outlet obstruction as determined by the investigator&#xD;
&#xD;
          9. Dilatation of the upper urinary tract&#xD;
&#xD;
         10. Low compliance bladder (Compliance &lt; 20 mL/cm H2O)&#xD;
&#xD;
         11. Detrusor hyporeflexia/areflexia and bradykinesia/tremor of the external urethral&#xD;
             sphincter&#xD;
&#xD;
         12. Prostatic or bladder carcinoma&#xD;
&#xD;
         13. Acute urinary tract infection during the run-in period or during study period&#xD;
&#xD;
         14. History of interstitial cystitis&#xD;
&#xD;
         15. Surgery of the prostate, the urinary bladder, the urethra, and thermotherapy,&#xD;
             ultrasound or laser therapy of the prostate for 12 months prior to enrolment to the&#xD;
             study&#xD;
&#xD;
         16. Pelvic radiation therapy&#xD;
&#xD;
         17. Use of indwelling catheter&#xD;
&#xD;
         18. Any electro stimulation therapy within the 14 days prior to inclusion visit 2&#xD;
&#xD;
         19. Significant hepatic or renal disease defined as twice the upper limit of the reference&#xD;
             range, regarding serum concentrations of Aspartate transaminase ((SGOT) (AST)),&#xD;
             Alanine transaminase ((SGPT) ALT)), Alkaline phosphatase (ALP), and/or creatinine &gt;&#xD;
             1.4 mg/dl&#xD;
&#xD;
         20. Diseases or any condition, in which treatment with ß3-adrenoceptors agonists is&#xD;
             contraindicated&#xD;
&#xD;
         21. Participation in another clinical trail 8 weeks preceding to enrolment in this study&#xD;
             or during study period&#xD;
&#xD;
         22. Patients with any severe medical or any other condition which in the opinion of the&#xD;
             investigator makes the patient unsuitable for inclusion&#xD;
&#xD;
         23. Allergic to KUC-7483 or its excipients&#xD;
&#xD;
         24. Patients with Diabetes mellitus type 1 or 2 treated with oral antidiabetic drugs or&#xD;
             insulin (any formulation)&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <link>
    <url>http://trials.boehringer-ingelheim.com</url>
    <description>Related Info</description>
  </link>
  <verification_date>October 2014</verification_date>
  <study_first_submitted>October 6, 2014</study_first_submitted>
  <study_first_submitted_qc>October 6, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 9, 2014</study_first_posted>
  <last_update_submitted>October 6, 2014</last_update_submitted>
  <last_update_submitted_qc>October 6, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 9, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spinal Cord Injuries</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02259751
org study id: 1207.4
nct id: NCT02259751
lead sponsor: 
Study to investigate pharmacodynamic effects and pharmacokinetics of KUC 7483
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Change from baseline in "volume at first contraction"
time frame: 2 hours post dosing
measure: Change from baseline in "volume at first contraction"
time frame: 6 hours post dosing
measure: Change from baseline in Detrusor pressure at first contraction
time frame: 2 and 6 hours post dosing
measure: Change from baseline in Maximum amplitude of involuntary detrusor contraction
time frame: 2 and 6 hours post dosing
measure: Change from baseline in Volume at first incontinence episode
time frame: 2 and 6 hours post dosing
measure: Change from baseline in compliance
time frame: 2 and 6 hours post dosing
measure: Change from baseline in Maximum cystometric capacity
time frame: 2 and 6 hours post dosing
measure: Change from baseline in Detrusor pressure at maximum flow induced by triggering
time frame: 2 and 6 hours post dosing
measure: Change from baseline in Post-triggering residual urinary volume
time frame: 2 and 6 hours post dosing
measure: AUC0-∞ (area under the concentration time curve of KUC 7322 ZW in plasma over the time interval from 0 extrapolated to infinity)
time frame: up to 24 hours post dosing
measure: Cmax (maximum concentration of KUC 7322 ZW in plasma)
time frame: up to 24 hours post dosing
measure: AUC0-tz (area under the concentration-time curve of KUC 7322 ZW in plasma over the time interval from 0 to the time of the last quantifiable data point)
time frame: up to 24 hours post dosing
measure: AUC0-24 (Area under the concentration time curve of KUC 7322 ZW in plasma over the time interval 0 to 24 hours)
time frame: up to 24 hours post dosing
measure: tmax (time from dosing to the maximum concentration of KUC 7322 ZW in plasma)
time frame: up to 24 hours post dosing
measure: λz (terminal rate constant of KUC 7322 ZW in plasma)
time frame: up to 24 hours post dosing
measure: t1/2 (terminal half-life of KUC 7322 ZW in plasma)
time frame: up to 24 hours post dosing
measure: MRTpo (mean residence time of KUC 7322 ZW in the body after po administration)
time frame: up to 24 hours post dosing
measure: CL/F (apparent clearance of KUC 7322 ZW in the plasma after extravascular administration)
time frame: up to 24 hours post dosing
measure: Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
time frame: up to 24 hours post dosing
measure: Aet1-t2 (amount of KUC 7322 ZW that is eliminated in urine from the time interval t1 to t2)
time frame: up to 24 hours post dosing
measure: fet1-t2 (fraction of administered drug excreted unchanged in urine from time point t1 to t2)
time frame: up to 24 hours post dosing
measure: CLR,t1-t2 (renal clearance of KUC 7322 ZW in plasma from the time point t1 until the time point t2)
time frame: up to 24 hours post dosing
measure: Number of patients with adverse events
time frame: up to 26 days
measure: Number of patients with clinically significant changes in vital signs
time frame: up to 24 hours post dosing
description: Blood Pressure
measure: Assessment of tolerability by investigator on a 4-point scale
time frame: 10 days post dosing
measure: Assessment of tolerability by patient on a 4-point scale
time frame: 10 days post dosing
arm group label: KUC 7483 CL
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: KUC 7483 CL
arm group label: KUC 7483 CL
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: Spinal Cord Injuries
mesh term: Wounds and Injuries