<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/NCT02240459</url>
  </required_header>
  <id_info>
    <org_study_id>FES-COG 1808</org_study_id>
    <nct_id>NCT02240459</nct_id>
  </id_info>
  <brief_title>A Study of Fesoterodine and Oxybutynin on Cognitive Function in Mild Cognitive Impairment</brief_title>
  <official_title>A Double Blind, Randomized Four Way Cross Over Study to Compare the Effect of Fesoterodine 4mg and 8mg Once Daily and Oxybutynin 5mg Twice Daily After Steady State Dosing Versus Placebo on Cognitive Function in Subjects With Overactive Bladder, Over the Age of 75 Years With Mild Cognitive Impairment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Alberta</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Alberta</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess the effects of fesoterodine at 4mg and 8mg doses&#xD;
      versus a placebo and oxybutynin 5mg bid versus placebo on cognitive abilities in older people&#xD;
      with overactive bladder and mild cognitive impairment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized placebo controlled, blinded four way cross over trial of the effect of&#xD;
      medications used to treat overactive bladder on the cognition of older men and women with&#xD;
      mild cognitive impairment. Each treatment phase is a week, with a weeks washout period before&#xD;
      starting the next treatment. Cognitive testing is by way of a validated computer assisted&#xD;
      battery of tests&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2016</start_date>
  <completion_date type="Actual">January 31, 2020</completion_date>
  <primary_completion_date type="Actual">January 31, 2020</primary_completion_date>
  <phase>Phase 2</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>continuity of attention</measure>
    <time_frame>1 and 4h post dose</time_frame>
    <description>Continuity of Attention:&#xD;
Accuracy of responding in Choice Reaction Time task Percent Target Detection in Digit Vigilance task False Alarms in Digit Vigilance task</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>cognitive function</measure>
    <time_frame>1 and 4h post last dose of study drug</time_frame>
    <description>includes the following domains of cognition&#xD;
power of attention,&#xD;
quality of working memory,&#xD;
quality of episodic secondary memory,&#xD;
speed of memory&#xD;
Montreal Cognitive assessment score</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>Overactive Bladder</condition>
  <condition>Mild Cognitive Impairment</condition>
  <arm_group>
    <arm_group_label>Fesoterodine 4mg daily</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>fesoterodine 4mg oral</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fesoterodine 8mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Fesoterodine 8mg in form of 2, 4mg tablets</description>
  </arm_group>
  <arm_group>
    <arm_group_label>oxybutynin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>oxybutynin immediate release, encapsulated 2, 5mg capsules daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo capsule</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>placebo capsule, 2 per day</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>fesoterodine 4mg</intervention_name>
    <description>7 days therapy followed by seven days washout. Each 4mg tablet is taken in the morning</description>
    <arm_group_label>Fesoterodine 4mg daily</arm_group_label>
    <arm_group_label>Fesoterodine 8mg</arm_group_label>
    <arm_group_label>oxybutynin</arm_group_label>
    <arm_group_label>placebo capsule</arm_group_label>
    <other_name>Toviaz</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxybutynin</intervention_name>
    <description>5mg IR oxybutynin taken bid, encapsulated into a form indistinguishable from placebo</description>
    <arm_group_label>Fesoterodine 4mg daily</arm_group_label>
    <arm_group_label>Fesoterodine 8mg</arm_group_label>
    <arm_group_label>oxybutynin</arm_group_label>
    <arm_group_label>placebo capsule</arm_group_label>
    <other_name>ditropan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>placebo capsule, one twice daily, and 2 placebo fesoterodine tablets taken each morning for masking and comparator purposes</description>
    <arm_group_label>Fesoterodine 4mg daily</arm_group_label>
    <arm_group_label>Fesoterodine 8mg</arm_group_label>
    <arm_group_label>oxybutynin</arm_group_label>
    <arm_group_label>placebo capsule</arm_group_label>
    <other_name>placebo capsule</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>fesoterodine 8mg</intervention_name>
    <description>2, 4mg fesoterodine capsules taken together in the morning</description>
    <arm_group_label>Fesoterodine 4mg daily</arm_group_label>
    <arm_group_label>Fesoterodine 8mg</arm_group_label>
    <arm_group_label>oxybutynin</arm_group_label>
    <arm_group_label>placebo capsule</arm_group_label>
    <other_name>Toviaz 8mg</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. The subject is either male or female and ≥ 75 years of age.&#xD;
&#xD;
          2. The subject has OAB as determined by ICS criteria&#xD;
&#xD;
          3. The subject has mild cognitive impairment as determined by NIA criteria&#xD;
&#xD;
          4. The subject is competent to give informed consent and perform the tasks associated&#xD;
             with the study&#xD;
&#xD;
          5. The subject has a body mass index (BMI) between 18.0 to 30.0 kg/m2 inclusive.&#xD;
&#xD;
          6. Written informed consent has been obtained.&#xD;
&#xD;
          7. The subject is available to complete the study.&#xD;
&#xD;
          8. At training visits (visit 2): the subject has performed at or above the minimum level&#xD;
             on at least one occasion for each individual task measure in cognitive function test&#xD;
             training.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. The subject does not have OAB.&#xD;
&#xD;
          2. The subject has either dementia or moderate to severe cognitive impairment at&#xD;
             screening.&#xD;
&#xD;
          3. The subject has probable clinical depression as determined by Geriatric Depression&#xD;
             Scale (GDS) short form &gt;5 at screening.&#xD;
&#xD;
          4. Subjects taking any cognitive enhancers (cholinesterase inhibitors or memantine).&#xD;
&#xD;
          5. The subject has a history of allergy to the study drug(s), to any component of the&#xD;
             dosage form or any other allergy, which, in the opinion of the Investigator,&#xD;
             contraindicates their participation.&#xD;
&#xD;
          6. The subject has any clinically significant abnormal heart rate or blood pressure&#xD;
             measurements, at the screening visit, which, in the opinion of the Investigator,&#xD;
             prevent safe participation in the study. (dBP&lt; 60mmHg or &gt; 90mmHg, sBP &lt; 95mmHg or &gt;&#xD;
             160mmHg or HR &lt; 40bpm or &gt; 100bpm).&#xD;
&#xD;
          7. Subjects with known history of urinary retention, severe gastrointestinal obstruction&#xD;
             (including paralytic ileus or intestinal atony) or severe gastrointestinal conditions&#xD;
             (including toxic megacolon or ulcerative colitis), myasthenia gravis, uncontrolled&#xD;
             narrow angle glaucoma or shallow interior chamber or subjects deemed to be at risk for&#xD;
             these conditions.&#xD;
&#xD;
          8. Subjects undergoing haemodialysis or who have severe renal impairment.&#xD;
&#xD;
          9. Subjects with severe hepatic impairment, defined as Child-Pugh grade IV.&#xD;
&#xD;
         10. Subjects taking potent CYP 3A4 inhibitors which would, under normal circumstances,&#xD;
             require adjustment of the dose of the test drugs.&#xD;
&#xD;
         11. Subject has taken prescribed medication within 14 days prior to the first study day or&#xD;
             over-the-counter medicine (including vitamins and herbal remedies) within 48 hours&#xD;
             prior to the first study day, which in the opinion of the Investigator, will interfere&#xD;
             with the study procedures or compromise safety.&#xD;
&#xD;
         12. Subject has an average weekly alcohol intake of greater than 21 units (male) or 14&#xD;
             units (female) within the 90 days prior to the study. 1 unit is 270cc of beer, 40cc of&#xD;
             spirits or 125cc of wine.&#xD;
&#xD;
         13. History of smoking more than 10 cigarettes (or the equivalent amount of tobacco) per&#xD;
             day within the 90 days prior to the study.&#xD;
&#xD;
         14. Subject has participated in any clinical study within the last 90 days.&#xD;
&#xD;
         15. Any clinically significant abnormality following Investigator review of the pre study&#xD;
             physical examination.&#xD;
&#xD;
         16. Any clinical condition, which, in the opinion of the Investigator, would not allow&#xD;
             safe completion of the study.&#xD;
&#xD;
         17. Any subjects who, in the opinion of the investigator, may find it difficult to adhere&#xD;
             to the provisions of treatment and observation specified in the protocol.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>75 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Adrian S Wagg, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Alberta</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Division of Geriatric Medicine, Clinical Sciences Building, University of Alberta Hosp</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 2P4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>Wagg A, Dale M, Tretter R, Stow B, Compion G. Randomised, multicentre, placebo-controlled, double-blind crossover study investigating the effect of solifenacin and oxybutynin in elderly people with mild cognitive impairment: the SENIOR study. Eur Urol. 2013 Jul;64(1):74-81. doi: 10.1016/j.eururo.2013.01.002. Epub 2013 Jan 11.</citation>
    <PMID>23332882</PMID>
  </reference>
  <reference>
    <citation>Wesnes KA, Edgar C, Tretter RN, Bolodeoku J. Exploratory pilot study assessing the risk of cognitive impairment or sedation in the elderly following single doses of solifenacin 10 mg. Expert Opin Drug Saf. 2009 Nov;8(6):615-26. doi: 10.1517/14740330903260790.</citation>
    <PMID>19747069</PMID>
  </reference>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>September 11, 2014</study_first_submitted>
  <study_first_submitted_qc>September 12, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 15, 2014</study_first_posted>
  <last_update_submitted>February 18, 2020</last_update_submitted>
  <last_update_submitted_qc>February 18, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Alberta</investigator_affiliation>
    <investigator_full_name>Adrian Wagg</investigator_full_name>
    <investigator_title>Research Chair in Healthy Aging</investigator_title>
  </responsible_party>
  <keyword>crossover study</keyword>
  <keyword>placebo controlled</keyword>
  <keyword>double blind</keyword>
  <keyword>overactive bladder</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Urinary Bladder, Overactive</mesh_term>
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fesoterodine</mesh_term>
    <mesh_term>Oxybutynin</mesh_term>
  </intervention_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/NCT02240459
org study id: FES-COG 1808
nct id: NCT02240459
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to assess the effects of fesoterodine at 4mg and 8mg doses
      versus a placebo and oxybutynin 5mg bid versus placebo on cognitive abilities in older people
      with overactive bladder and mild cognitive impairment.
This is a randomized placebo controlled, blinded four way cross over trial of the effect of
      medications used to treat overactive bladder on the cognition of older men and women with
      mild cognitive impairment. Each treatment phase is a week, with a weeks washout period before
      starting the next treatment. Cognitive testing is by way of a validated computer assisted
      battery of tests
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: continuity of attention
time frame: 1 and 4h post dose
description: Continuity of Attention:
Accuracy of responding in Choice Reaction Time task Percent Target Detection in Digit Vigilance task False Alarms in Digit Vigilance task
measure: cognitive function
time frame: 1 and 4h post last dose of study drug
description: includes the following domains of cognition
power of attention,
quality of working memory,
quality of episodic secondary memory,
speed of memory
Montreal Cognitive assessment score
arm group label: Fesoterodine 4mg daily
arm group type: Experimental
description: fesoterodine 4mg oral
arm group label: Fesoterodine 8mg
arm group type: Experimental
description: Fesoterodine 8mg in form of 2, 4mg tablets
arm group label: oxybutynin
arm group type: Active Comparator
description: oxybutynin immediate release, encapsulated 2, 5mg capsules daily
arm group label: placebo capsule
arm group type: Placebo Comparator
description: placebo capsule, 2 per day
intervention type: Drug
intervention name: fesoterodine 4mg
description: 7 days therapy followed by seven days washout. Each 4mg tablet is taken in the morning
arm group label: Fesoterodine 4mg daily
arm group label: Fesoterodine 8mg
arm group label: oxybutynin
arm group label: placebo capsule
other name: Toviaz
intervention type: Drug
intervention name: Oxybutynin
description: 5mg IR oxybutynin taken bid, encapsulated into a form indistinguishable from placebo
arm group label: Fesoterodine 4mg daily
arm group label: Fesoterodine 8mg
arm group label: oxybutynin
arm group label: placebo capsule
other name: ditropan
intervention type: Drug
intervention name: placebo
description: placebo capsule, one twice daily, and 2 placebo fesoterodine tablets taken each morning for masking and comparator purposes
arm group label: Fesoterodine 4mg daily
arm group label: Fesoterodine 8mg
arm group label: oxybutynin
arm group label: placebo capsule
other name: placebo capsule
intervention type: Drug
intervention name: fesoterodine 8mg
description: 2, 4mg fesoterodine capsules taken together in the morning
arm group label: Fesoterodine 4mg daily
arm group label: Fesoterodine 8mg
arm group label: oxybutynin
arm group label: placebo capsule
other name: Toviaz 8mg
criteria: 
gender: All
minimum age: 75 Years
maximum age: N/A
healthy volunteers: No
last name: Adrian S Wagg, MD
role: Principal Investigator
affiliation: University of Alberta
facility: 
country: Canada
citation: Wagg A, Dale M, Tretter R, Stow B, Compion G. Randomised, multicentre, placebo-controlled, double-blind crossover study investigating the effect of solifenacin and oxybutynin in elderly people with mild cognitive impairment: the SENIOR study. Eur Urol. 2013 Jul;64(1):74-81. doi: 10.1016/j.eururo.2013.01.002. Epub 2013 Jan 11.
PMID: 23332882
citation: Wesnes KA, Edgar C, Tretter RN, Bolodeoku J. Exploratory pilot study assessing the risk of cognitive impairment or sedation in the elderly following single doses of solifenacin 10 mg. Expert Opin Drug Saf. 2009 Nov;8(6):615-26. doi: 10.1517/14740330903260790.
PMID: 19747069
responsible party type: Principal Investigator
investigator affiliation: University of Alberta
investigator full name: Adrian Wagg
investigator title: Research Chair in Healthy Aging
mesh term: Urinary Bladder, Overactive
mesh term: Cognitive Dysfunction
mesh term: Fesoterodine
mesh term: Oxybutynin