<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/NCT01729819</url>
  </required_header>
  <id_info>
    <org_study_id>000085</org_study_id>
    <nct_id>NCT01729819</nct_id>
  </id_info>
  <brief_title>Interventional Clinical Trial in Patients in Overactive Bladder With Nocturia in Women</brief_title>
  <official_title>A Multi-centre, Double-blind, Randomised Trial Investigating the Efficacy and Safety of a Combination Therapy, Desmopressin and Tolterodine, for Treatment of Overactive Bladder With Nocturia in Women</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ferring Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ferring Pharmaceuticals</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the trial is to investigate the efficacy of combining tolterodine and&#xD;
      desmopressin compared with tolterodine monotherapy in the treatment of women with overactive&#xD;
      bladder with nocturia in terms of reduction of nocturnal voids during 3 months of treatment&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">November 2014</completion_date>
  <primary_completion_date type="Actual">November 2014</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Mean Number of Nocturnal Voids From Baseline</measure>
    <time_frame>Baseline to 3 months of treatment</time_frame>
    <description>A nocturnal void was defined as a void occurring at least 5 minutes after going to bed, but before getting up the next morning. The mean estimate was the average over 3 consecutive 24-hour periods prior to the respective visit as captured in the voiding and sleep diary.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Mean Time to First Nocturnal Void From Baseline</measure>
    <time_frame>Baseline to 3 months of treatment</time_frame>
    <description>The time to first nocturnal void was defined as the time from going to bed with the intention of sleeping until first nocturnal void or until waking in the morning in the case there is no nocturnal void. The time to first void was calculated as the average over three consecutive 24-hour periods prior to the respective visits.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Mean Nocturnal Urine Volume From Baseline</measure>
    <time_frame>Baseline to 3 months of treatment</time_frame>
    <description>The mean nocturnal urine volume was derived from the three-day urine volume diary. The nocturnal volume was defined as the sum of the volumes for all nocturnal voids including the volume of the first morning void within 30 min of waking up in the morning.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Responder Status</measure>
    <time_frame>Baseline to 3 months of treatment</time_frame>
    <description>Responder status was defined as ≥33% decrease in the mean number of nocturnal void and at least one night with no voids out of the 3-day diary period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Onset of Effect as Seen in Change in Mean Number of Nocturnal Voids From Baseline for Each Visit During Three Months of Treatment</measure>
    <time_frame>Baseline to 3 months of treatment</time_frame>
    <description>A nocturnal void was defined as a void occurring at least 5 minutes after going to bed, but before getting up the next morning. The mean estimate was the average over 3 consecutive 24-hour periods prior to the respective visit as captured in the voiding and sleep diary.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the Impact on Sleep as Measured by the Sleep Rating Scales From Baseline</measure>
    <time_frame>Baseline to 3 months of treatment</time_frame>
    <description>An electronic diary was used in the trial to document the impact on sleep quality (sleep rating scales). The sleep rating scales included three questions that ranged from 0 (poor) to 10 (good). The average of each question for each visit was summarised and the change from baseline was analysed longitudinally during the three months of treatment.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">106</enrollment>
  <condition>Overactive Bladder</condition>
  <arm_group>
    <arm_group_label>Combination</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tolterodine tartrate extended release capsules + Desmopressin orally disintegrating tablets</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tolterodine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Tolterodine tartrate extended release capsules + Placebo orally disintegrating tablets</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tolterodine tartrate extended release capsules</intervention_name>
    <arm_group_label>Combination</arm_group_label>
    <arm_group_label>Tolterodine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Desmopressin orally disintegrating tablets</intervention_name>
    <arm_group_label>Combination</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo orally disintegrating tablets</intervention_name>
    <arm_group_label>Tolterodine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent prior to performance of any trial-related activity&#xD;
&#xD;
          -  Female sex, at least 18 years of age (at the time of written consent)&#xD;
&#xD;
          -  Nocturia and overactive bladder symptoms present for ≥6 months prior to trial entry&#xD;
             (patient-reported)&#xD;
&#xD;
          -  At least 2 nocturnal voids each night as documented in 2 diary periods during the&#xD;
             screening. A mean of at least 8 daytime voids per day over 3 days with a minimum of at&#xD;
             least 6 daytime voids each day as documented in 2 diary periods during the screening.&#xD;
             At least 1 urgency episode each 24 hours as documented in 2 diary periods during the&#xD;
             screening. Each diary period consists of 3 consecutive days, with at least 14 days&#xD;
             between each period.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Evidence of severe voiding dysfunction defined as:&#xD;
&#xD;
        More than 10 nocturnal voids per 24 hours as documented on any of the days in both diary&#xD;
        periods during screening.&#xD;
&#xD;
        More than 20 daytime voids per 24 hours as documented on any of the days in both diary&#xD;
        periods during screening.&#xD;
&#xD;
          -  Genito-urinary tract pathology that can in the investigator's opinion be responsible&#xD;
             for urgency or urinary incontinence e.g., symptomatic or recurrent urinary tract&#xD;
             infections, interstitial cystitis, bladder related pain, or stone in the bladder and&#xD;
             urethra causing symptoms&#xD;
&#xD;
          -  Current or a history within 5 years of lower urologic malignancies (e.g., bladder&#xD;
             cancer), lower urinary tract surgery, previous pelvic irradiation, or severe&#xD;
             neurological disease affecting bladder function or muscle strength (e.g., multiple&#xD;
             sclerosis, Parkinson's disease, spinal cord injury, spina bifida)&#xD;
&#xD;
          -  Symptoms of severe stress urinary incontinence in the opinion of the investigator&#xD;
&#xD;
          -  Urinary retention or a post void residual volume in excess of 150 mL as confirmed by&#xD;
             bladder ultrasound performed after suspicion of urinary retention&#xD;
&#xD;
          -  Habitual or psychogenic polydipsia (fluid intake resulting in a urine production&#xD;
             exceeding 40 mL/kg/24 hours) or a mean volume voided per void of 350 mL or more during&#xD;
             one or more 24-hour periods as assessed by the screening diaries&#xD;
&#xD;
          -  Central or nephrogenic diabetes insipidus&#xD;
&#xD;
          -  Syndrome of inappropriate antidiuretic hormone (SIADH)&#xD;
&#xD;
          -  Gastric retention&#xD;
&#xD;
          -  Myasthenia gravis&#xD;
&#xD;
          -  Uncontrolled narrow-angle glaucoma&#xD;
&#xD;
          -  Suspicion or evidence of cardiac failure&#xD;
&#xD;
          -  Uncontrolled and clinically relevant (in the judgement of the investigator)&#xD;
             hypertension or diabetes mellitus&#xD;
&#xD;
          -  History and/or current treatment of obstructive sleep apnoea&#xD;
&#xD;
          -  Hyponatraemia:Serum sodium level must not be below 135 mmol/L&#xD;
&#xD;
          -  Evidence of potential renal impairment:Serum creatinine must be within normal&#xD;
             laboratory reference intervals AND estimated glomerular filtration rate must be more&#xD;
             than or equal to 50 mL/min&#xD;
&#xD;
          -  Hepatic and/or biliary diseases: Aspartate aminotransferase and/or alanine&#xD;
             aminotransferase levels must not be more than twice the upper limit of normal range.&#xD;
             Total bilirubin level must not be more than 1.5 mg/dL&#xD;
&#xD;
          -  Pregnancy, breastfeeding, or a plan to become pregnant during the period of the trial.&#xD;
             Women of reproductive age must have documentation of a reliable method of&#xD;
             contraception. All pre- and perimenopausal women have to perform pregnancy tests.&#xD;
             Amenorrhea of more than 12 months duration based on the reported date of the last&#xD;
             menstrual period is sufficient documentation of post-menopausal status and does not&#xD;
             require a pregnancy test&#xD;
&#xD;
          -  Known alcohol or substance abuse; work or lifestyle that may interfere with regular&#xD;
             night-time sleep e.g., shift workers; or any other medical condition, laboratory&#xD;
             abnormality, psychiatric condition, mental incapacity, illiteracy or language barrier&#xD;
             which, in the judgement of the investigator, would impair participation in the trial&#xD;
&#xD;
          -  Known or suspected hypersensitivity to any active ingredient or excipients in the&#xD;
             investigational medicinal products used in the trial&#xD;
&#xD;
          -  Previous participation in any desmopressin trial within the last 5 years&#xD;
&#xD;
          -  Use of any prohibited therapy, as defined in the protocol&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Development Support</last_name>
    <role>Study Director</role>
    <affiliation>Ferring Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>NEA Baptist Clinic</name>
      <address>
        <city>Jonesboro</city>
        <state>Arkansas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lynn Institute of The Ozarks</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Moez Khorsandi, DO</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Urology Group of Southern California</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Riverside Clinical Research</name>
      <address>
        <city>Edgewater</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Health Awareness, Inc.</name>
      <address>
        <city>Jupiter</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pines Clinical Research, Inc.</name>
      <address>
        <city>Pembroke Pines</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Palm Beach Research Center</name>
      <address>
        <city>West Palm Beach</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research Atlanta</name>
      <address>
        <city>Stockbridge</city>
        <state>Georgia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northshore Center for Gastroenterology</name>
      <address>
        <city>Evanston</city>
        <state>Illinois</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Remedica, LLC</name>
      <address>
        <city>Rochester</city>
        <state>Michigan</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Urological Institute of Northeastern New York</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Premier Medical Group of the Hudson Valley, P.C.</name>
      <address>
        <city>Poughkeepsie</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Parkhurst Research Organization, LLC</name>
      <address>
        <city>Bethany</city>
        <state>Oklahoma</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Philadelphia Clinical Research, LLC</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Coastal Carolina Research Center</name>
      <address>
        <city>Mount Pleasant</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Across America</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advances in Health</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pioneer Research Solutions, Inc.</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Radiant Research</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research Associates of Tidewater</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seattle Women's: Health, Research, Gynecology</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>November 15, 2012</study_first_submitted>
  <study_first_submitted_qc>November 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 20, 2012</study_first_posted>
  <results_first_submitted>July 20, 2018</results_first_submitted>
  <results_first_submitted_qc>July 20, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">August 14, 2018</results_first_posted>
  <disposition_first_submitted>November 2, 2015</disposition_first_submitted>
  <disposition_first_submitted_qc>November 2, 2015</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">November 30, 2015</disposition_first_posted>
  <last_update_submitted>August 16, 2018</last_update_submitted>
  <last_update_submitted_qc>August 16, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">September 12, 2018</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>Urinary Bladder, Overactive</mesh_term>
    <mesh_term>Nocturia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Deamino Arginine Vasopressin</mesh_term>
    <mesh_term>Tolterodine Tartrate</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This was a multi-centre trial conducted in the US. A total of 33 sites were initiated in this trial, and of these eligible patients from 20 sites were randomised to a treatment. The first patient first visit was on 28 January 2013. The last patient last visit was on 19 November 2014.</recruitment_details>
      <pre_assignment_details>The trial was initiated with a screening period of 3-4 weeks between Visits 1 and 2a, where no investigational medicinal product was taken. Patients who were on a prohibited medication and needed a wash-out period of 1-2 weeks initiated the trial at Visit 0. Eligible patients were randomised to one of the two treatment groups at Visit 2a.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Combination</title>
          <description>Tolterodine tartrate extended release capsules (4 mg) + Desmopressin orally disintegrating tablets (25 μg)&#xD;
Tolterodine tartrate extended release capsules&#xD;
Desmopressin orally disintegrating tablets</description>
        </group>
        <group group_id="P2">
          <title>Tolterodine</title>
          <description>Tolterodine tartrate extended release capsules (4 mg) + Placebo orally disintegrating tablets&#xD;
Tolterodine tartrate extended release capsules&#xD;
Placebo orally disintegrating tablets</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="49"/>
                <participants group_id="P2" count="57"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="43"/>
                <participants group_id="P2" count="50"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other reason</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The Full Analysis Set (FAS) comprised of all randomised and exposed subjects with at least one efficacy assessment after treatment initiation.The FAS comprised of 97 subjects (45 in the combination group and 52 in the tolterodine group). All analyses were done based on the FAS.</population>
      <group_list>
        <group group_id="B1">
          <title>Combination</title>
          <description>Tolterodine tartrate extended release capsules (4 mg) + Desmopressin orally disintegrating tablets (25 µg)&#xD;
Tolterodine tartrate extended release capsules&#xD;
Desmopressin orally disintegrating tablets</description>
        </group>
        <group group_id="B2">
          <title>Tolterodine</title>
          <description>Tolterodine tartrate extended release capsules (4 mg)+ Placebo orally disintegrating tablets&#xD;
Tolterodine tartrate extended release capsules&#xD;
Placebo orally disintegrating tablets</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="45"/>
            <count group_id="B2" value="52"/>
            <count group_id="B3" value="97"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="55.3" spread="12.6"/>
                    <measurement group_id="B2" value="51.8" spread="10.3"/>
                    <measurement group_id="B3" value="53.4" spread="11.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="45"/>
                    <measurement group_id="B2" value="52"/>
                    <measurement group_id="B3" value="97"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                    <measurement group_id="B2" value="42"/>
                    <measurement group_id="B3" value="75"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="73"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Mean Number of Nocturnal Voids</title>
          <units>Voids</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3.38" spread="0.97"/>
                    <measurement group_id="B2" value="3.11" spread="1.06"/>
                    <measurement group_id="B3" value="3.24" spread="1.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Mean Number of Day time Voids</title>
          <units>Voids</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9.69" spread="1.35"/>
                    <measurement group_id="B2" value="10.1" spread="1.97"/>
                    <measurement group_id="B3" value="9.91" spread="1.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Mean Nocturnal Urine Volume</title>
          <units>mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="546" spread="281"/>
                    <measurement group_id="B2" value="537" spread="278"/>
                    <measurement group_id="B3" value="541" spread="278"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Mean Time to First Nocturnal Void</title>
          <units>Minutes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="125" spread="44.6"/>
                    <measurement group_id="B2" value="143" spread="56.1"/>
                    <measurement group_id="B3" value="135" spread="51.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Mean Number of Nocturnal Voids From Baseline</title>
        <description>A nocturnal void was defined as a void occurring at least 5 minutes after going to bed, but before getting up the next morning. The mean estimate was the average over 3 consecutive 24-hour periods prior to the respective visit as captured in the voiding and sleep diary.</description>
        <time_frame>Baseline to 3 months of treatment</time_frame>
        <population>The FAS comprised of all randomised and exposed subjects with at least one efficacy assessment after treatment initiation. The FAS comprised of 97 subjects (45 in the combination group and 52 in the tolterodine group).</population>
        <group_list>
          <group group_id="O1">
            <title>Combination</title>
            <description>Tolterodine tartrate extended release capsules (4 mg)+ Desmopressin orally disintegrating tablets (25 μg)&#xD;
Tolterodine tartrate extended release capsules&#xD;
Desmopressin orally disintegrating tablets</description>
          </group>
          <group group_id="O2">
            <title>Tolterodine</title>
            <description>Tolterodine tartrate extended release capsules (4 mg) + Placebo orally disintegrating tablets&#xD;
Tolterodine tartrate extended release capsules&#xD;
Placebo orally disintegrating tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Mean Number of Nocturnal Voids From Baseline</title>
          <description>A nocturnal void was defined as a void occurring at least 5 minutes after going to bed, but before getting up the next morning. The mean estimate was the average over 3 consecutive 24-hour periods prior to the respective visit as captured in the voiding and sleep diary.</description>
          <population>The FAS comprised of all randomised and exposed subjects with at least one efficacy assessment after treatment initiation. The FAS comprised of 97 subjects (45 in the combination group and 52 in the tolterodine group).</population>
          <units>Voids</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="45"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.63" lower_limit="-1.94" upper_limit="-1.32"/>
                    <measurement group_id="O2" value="-1.29" lower_limit="-1.57" upper_limit="-1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Combination versus tolterodine (i.e. effect in combination group minus effect in tolterodine group) is presented. The trial was to be declared positive if a statistically significant (two-sided, p &lt; 0.05) positive effect for combining tolterodine and desmopressin compared to tolterodine monotherapy on the primary endpoint had been demonstrated.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>The change in mean nocturnal voids from baseline as the dependent variable, baseline mean nocturnal voids as a covariate, and treatments and visit (Month 1, Month 2, and Month 3) as factors, was considered for the analysis. Longitudinal analysis based on repeated measures using analysis of covariance with subject as random effect. Missing values post-baseline were not imputed.</non_inferiority_desc>
            <p_value>0.112</p_value>
            <method>ANCOVA</method>
            <method_desc>Change in mean nocturnal voids as the dependent variable and baseline mean nocturnal voids as a covariate, treatment and visit as factors.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.34</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.77</ci_lower_limit>
            <ci_upper_limit>0.08</ci_upper_limit>
            <estimate_desc>Longitudinal analysis based on repeated measures using analysis of covariance with subject as random effect. The estimated value represents the contrast of combination - tolterodine.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Mean Time to First Nocturnal Void From Baseline</title>
        <description>The time to first nocturnal void was defined as the time from going to bed with the intention of sleeping until first nocturnal void or until waking in the morning in the case there is no nocturnal void. The time to first void was calculated as the average over three consecutive 24-hour periods prior to the respective visits.</description>
        <time_frame>Baseline to 3 months of treatment</time_frame>
        <population>The FAS comprised of all randomised and exposed subjects with at least one efficacy assessment after treatment initiation. The FAS comprised of 97 subjects (45 in the combination group and 52 in the tolterodine group).</population>
        <group_list>
          <group group_id="O1">
            <title>Combination</title>
            <description>Tolterodine tartrate extended release capsules (4 mg) + Desmopressin orally disintegrating tablets (25 μg)&#xD;
Tolterodine tartrate extended release capsules&#xD;
Desmopressin orally disintegrating tablets</description>
          </group>
          <group group_id="O2">
            <title>Tolterodine</title>
            <description>Tolterodine tartrate extended release capsules (4 mg) + Placebo orally disintegrating tablets&#xD;
Tolterodine tartrate extended release capsules&#xD;
Placebo orally disintegrating tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Mean Time to First Nocturnal Void From Baseline</title>
          <description>The time to first nocturnal void was defined as the time from going to bed with the intention of sleeping until first nocturnal void or until waking in the morning in the case there is no nocturnal void. The time to first void was calculated as the average over three consecutive 24-hour periods prior to the respective visits.</description>
          <population>The FAS comprised of all randomised and exposed subjects with at least one efficacy assessment after treatment initiation. The FAS comprised of 97 subjects (45 in the combination group and 52 in the tolterodine group).</population>
          <units>Minutes</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="45"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="118.19" lower_limit="88.53" upper_limit="147.85"/>
                    <measurement group_id="O2" value="100.19" lower_limit="72.67" upper_limit="127.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Combination versus tolterodine (i.e. effect in combination group minus effect in tolterodine group) is presented.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.385</p_value>
            <method>ANCOVA</method>
            <method_desc>Change in mean time to first void as dependent variable and baseline mean time to first void as a covariate, and treatment and visit as factors.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>18</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-22.96</ci_lower_limit>
            <ci_upper_limit>58.96</ci_upper_limit>
            <estimate_desc>The estimated value represents the contrast of combination - tolterodine.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Mean Nocturnal Urine Volume From Baseline</title>
        <description>The mean nocturnal urine volume was derived from the three-day urine volume diary. The nocturnal volume was defined as the sum of the volumes for all nocturnal voids including the volume of the first morning void within 30 min of waking up in the morning.</description>
        <time_frame>Baseline to 3 months of treatment</time_frame>
        <population>The FAS comprised of all randomised and exposed subjects with at least one efficacy assessment after treatment initiation. The FAS comprised of 97 subjects (45 in the combination group and 52 in the tolterodine group).</population>
        <group_list>
          <group group_id="O1">
            <title>Combination</title>
            <description>Tolterodine tartrate extended release capsules (4 mg) + Desmopressin orally disintegrating tablets (25 µg)&#xD;
Tolterodine tartrate extended release capsules&#xD;
Desmopressin orally disintegrating tablets</description>
          </group>
          <group group_id="O2">
            <title>Tolterodine</title>
            <description>Tolterodine tartrate extended release capsules (4 mg) + Placebo orally disintegrating tablets&#xD;
Tolterodine tartrate extended release capsules&#xD;
Placebo orally disintegrating tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Mean Nocturnal Urine Volume From Baseline</title>
          <description>The mean nocturnal urine volume was derived from the three-day urine volume diary. The nocturnal volume was defined as the sum of the volumes for all nocturnal voids including the volume of the first morning void within 30 min of waking up in the morning.</description>
          <population>The FAS comprised of all randomised and exposed subjects with at least one efficacy assessment after treatment initiation. The FAS comprised of 97 subjects (45 in the combination group and 52 in the tolterodine group).</population>
          <units>mL</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="45"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-156.6" lower_limit="-212.88" upper_limit="-100.37"/>
                    <measurement group_id="O2" value="-92.46" lower_limit="-145.27" upper_limit="-39.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Combination versus tolterodine (i.e. effect in combination group minus effect in tolterodine group) is presented</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.103</p_value>
            <method>ANCOVA</method>
            <method_desc>Change in mean nocturnal volume as the dependent variable and baseline mean nocturnal volume as a covariate, and treatment and visit as factors.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-64.16</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-141.46</ci_lower_limit>
            <ci_upper_limit>13.14</ci_upper_limit>
            <estimate_desc>The estimated value represents the contrast of combination - tolterodine.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Responder Status</title>
        <description>Responder status was defined as ≥33% decrease in the mean number of nocturnal void and at least one night with no voids out of the 3-day diary period.</description>
        <time_frame>Baseline to 3 months of treatment</time_frame>
        <population>The FAS comprised of all randomised and exposed subjects with at least one efficacy assessment after treatment initiation. The FAS comprised of 97 subjects (45 in the combination group and 52 in the tolterodine group).</population>
        <group_list>
          <group group_id="O1">
            <title>Combination</title>
            <description>Tolterodine tartrate extended release capsules (4 mg) + Desmopressin orally disintegrating tablets (25 µg)&#xD;
Tolterodine tartrate extended release capsules&#xD;
Desmopressin orally disintegrating tablets</description>
          </group>
          <group group_id="O2">
            <title>Tolterodine</title>
            <description>Tolterodine tartrate extended release capsules (4 mg) + Placebo orally disintegrating tablets&#xD;
Tolterodine tartrate extended release capsules&#xD;
Placebo orally disintegrating tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Responder Status</title>
          <description>Responder status was defined as ≥33% decrease in the mean number of nocturnal void and at least one night with no voids out of the 3-day diary period.</description>
          <population>The FAS comprised of all randomised and exposed subjects with at least one efficacy assessment after treatment initiation. The FAS comprised of 97 subjects (45 in the combination group and 52 in the tolterodine group).</population>
          <units>Proportion of responders</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="45"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.40"/>
                    <measurement group_id="O2" value="0.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Combination versus tolterodine (i.e. odds of being responder in combination group versus odds of being responder in tolterodine group) is presented. The proportion of responders during three months of treatment was analysed (i.e. the odds ratio of the odds of being a responder) longitudinally using Generalised Estimating Equation (GEE) for a repeated logistic regression.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.352</p_value>
            <p_value_desc>33% responder status as dependent variable, baseline mean nocturnal voids as covariate, treatment, and visit as factors.</p_value_desc>
            <method>Generalized Estimating Equation</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.36</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.71</ci_lower_limit>
            <ci_upper_limit>2.62</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Onset of Effect as Seen in Change in Mean Number of Nocturnal Voids From Baseline for Each Visit During Three Months of Treatment</title>
        <description>A nocturnal void was defined as a void occurring at least 5 minutes after going to bed, but before getting up the next morning. The mean estimate was the average over 3 consecutive 24-hour periods prior to the respective visit as captured in the voiding and sleep diary.</description>
        <time_frame>Baseline to 3 months of treatment</time_frame>
        <population>The FAS comprised of all randomised and exposed subjects with at least one efficacy assessment after treatment initiation. The FAS comprised of 97 subjects (45 in the combination group and 52 in the tolterodine group).</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment Difference (Combination-tolterodine)</title>
            <description>Change in mean number of nocturnal voids between combination (desmopressin [25 µg] + tolterodine [4 mg]) and tolterodine (4 mg) was estimated at month 1, month 2, month 3 and overall during the three months</description>
          </group>
        </group_list>
        <measure>
          <title>Onset of Effect as Seen in Change in Mean Number of Nocturnal Voids From Baseline for Each Visit During Three Months of Treatment</title>
          <description>A nocturnal void was defined as a void occurring at least 5 minutes after going to bed, but before getting up the next morning. The mean estimate was the average over 3 consecutive 24-hour periods prior to the respective visit as captured in the voiding and sleep diary.</description>
          <population>The FAS comprised of all randomised and exposed subjects with at least one efficacy assessment after treatment initiation. The FAS comprised of 97 subjects (45 in the combination group and 52 in the tolterodine group).</population>
          <units>Voids</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Month 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.19" lower_limit="-0.68" upper_limit="0.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.44" lower_limit="-0.95" upper_limit="0.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.43" lower_limit="-0.86" upper_limit="0.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Overall (during the three months)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.35" lower_limit="-0.78" upper_limit="0.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Treatment difference (Combination-tolterodine) at Month 1</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Estimated contrast (Combination - tolterodine) from longitudinal analysis including a treatment-by visit interaction term</non_inferiority_desc>
            <p_value>0.443</p_value>
            <p_value_desc>Adjusted treatment difference (Combination-tolterodine) in mean number of nocturnal voids at Month 1</p_value_desc>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Treatment difference (Combination-tolterodine) at Month 2</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Estimated contrast (Combination - tolterodine) from longitudinal analysis including a treatment-by visit interaction term</non_inferiority_desc>
            <p_value>0.086</p_value>
            <p_value_desc>Adjusted treatment difference in mean number of nocturnal voids (Combination-tolterodine) at Month 2</p_value_desc>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Treatment difference (Combination-tolterodine) at Month 3</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Estimated contrast (Combination - tolterodine) from longitudinal analysis including a treatment-by visit interaction term</non_inferiority_desc>
            <p_value>0.055</p_value>
            <p_value_desc>Adjusted treatment difference (Combination-tolterodine) in mean number of nocturnal voids at Month 3</p_value_desc>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Treatment difference (Combination-tolterodine) for the duration of 3 months</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Estimated contrast (Combination - tolterodine) from longitudinal analysis including a treatment-by visit interaction term</non_inferiority_desc>
            <p_value>0.106</p_value>
            <p_value_desc>Adjusted treatment difference (Combination-tolterodine) in mean number of nocturnal voids for the duration of 3 months</p_value_desc>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in the Impact on Sleep as Measured by the Sleep Rating Scales From Baseline</title>
        <description>An electronic diary was used in the trial to document the impact on sleep quality (sleep rating scales). The sleep rating scales included three questions that ranged from 0 (poor) to 10 (good). The average of each question for each visit was summarised and the change from baseline was analysed longitudinally during the three months of treatment.</description>
        <time_frame>Baseline to 3 months of treatment</time_frame>
        <population>The FAS comprised of all randomised and exposed subjects with at least one efficacy assessment after treatment initiation. The FAS comprised of 97 subjects (45 in the combination group and 52 in the tolterodine group).</population>
        <group_list>
          <group group_id="O1">
            <title>Combination</title>
            <description>Tolterodine tartrate extended release capsules (4 mg) + Desmopressin orally disintegrating tablets (25 µg)&#xD;
Tolterodine tartrate extended release capsules&#xD;
Desmopressin orally disintegrating tablets</description>
          </group>
          <group group_id="O2">
            <title>Tolterodine</title>
            <description>Tolterodine tartrate extended release capsules (4 mg) + Placebo orally disintegrating tablets&#xD;
Tolterodine tartrate extended release capsules&#xD;
Placebo orally disintegrating tablets</description>
          </group>
        </group_list>
        <measure>
          <title>Change in the Impact on Sleep as Measured by the Sleep Rating Scales From Baseline</title>
          <description>An electronic diary was used in the trial to document the impact on sleep quality (sleep rating scales). The sleep rating scales included three questions that ranged from 0 (poor) to 10 (good). The average of each question for each visit was summarised and the change from baseline was analysed longitudinally during the three months of treatment.</description>
          <population>The FAS comprised of all randomised and exposed subjects with at least one efficacy assessment after treatment initiation. The FAS comprised of 97 subjects (45 in the combination group and 52 in the tolterodine group).</population>
          <units>Score on scale</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="45"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>From very tired to wide awake, how do you feel now</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.76" lower_limit="1.31" upper_limit="2.21"/>
                    <measurement group_id="O2" value="1.33" lower_limit="0.91" upper_limit="1.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rate how refreshed you feel now</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.81" lower_limit="1.37" upper_limit="2.24"/>
                    <measurement group_id="O2" value="1.46" lower_limit="1.06" upper_limit="1.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rate the quality of your sleep last night</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.95" lower_limit="1.52" upper_limit="2.39"/>
                    <measurement group_id="O2" value="1.67" lower_limit="1.27" upper_limit="2.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Combination versus tolterodine (i.e. score on scale in combination group versus score on scale in tolterodine group) is presented.Statistical analysis for &quot;from very tired to wide awake, how do you feel now&quot;</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.178</p_value>
            <method>ANCOVA</method>
            <method_desc>Quality of sleep rating score as dependent variable, baseline quality of sleep rating scale value as a covariate, and responder status as a factor.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.42</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.20</ci_lower_limit>
            <ci_upper_limit>1.05</ci_upper_limit>
            <estimate_desc>Estimated contrast (Combination - tolterodine) from longitudinal analysis of covariance</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Combination versus tolterodine (i.e. score on scale in combination group versus score on scale in tolterodine group) is presented. Statistical analysis for &quot;Rate how refreshed you feel now&quot;</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.257</p_value>
            <method>ANCOVA</method>
            <method_desc>Quality of sleep rating score as dependent variable, baseline quality of sleep rating scale value as a covariate, and responder status as a factor.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.34</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.26</ci_lower_limit>
            <ci_upper_limit>0.94</ci_upper_limit>
            <estimate_desc>Estimated contrast (Combination - tolterodine) from longitudinal analysis of covariance</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Combination versus tolterodine (i.e. score on scale in combination group versus score on scale in tolterodine group) is presented. Statistical analysis for &quot;Rate the quality of your sleep last night&quot;</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Quality of sleep rating score as dependent variable, baseline quality of sleep rating scale value as a covariate, and responder status as a factor.</non_inferiority_desc>
            <p_value>0.360</p_value>
            <method>ANCOVA</method>
            <method_desc>Longitudinal analysis of covariance on change from baseline with baseline as a covariate, and treatment and visit as factors.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.28</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.32</ci_lower_limit>
            <ci_upper_limit>0.88</ci_upper_limit>
            <estimate_desc>Estimated contrast (Combination - tolterodine) from longitudinal analysis of covariance</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>3 months</time_frame>
      <desc>The safety analysis set included all patients who received at least one dose of IMP and had at least one safety assessment. The safety analysis set comprised of 103 patients (48 in the combination group and 55 in the tolterodine group).</desc>
      <group_list>
        <group group_id="E1">
          <title>Combination</title>
          <description>Tolterodine tartrate extended release capsules + Desmopressin orally disintegrating tablets&#xD;
Tolterodine tartrate extended release capsules&#xD;
Desmopressin orally disintegrating tablets</description>
        </group>
        <group group_id="E2">
          <title>Tolterodine</title>
          <description>Tolterodine tartrate extended release capsules + Placebo orally disintegrating tablets&#xD;
Tolterodine tartrate extended release capsules&#xD;
Placebo orally disintegrating tablets</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="55"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="55"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 16.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="48"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="55"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="55"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="48"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="55"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the Sponsor can review the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the Sponsor or confidential to the sponsor. Comments will be given within four weeks from receipt of the draft manuscript. Additional time may be required to allow the Sponsor to seek patent protection of the invention.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Clinical Development Support</name_or_title>
      <organization>Ferring Pharmaceuticals</organization>
      <email>DK0-Disclosure@ferring.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01729819
org study id: 000085
nct id: NCT01729819
lead sponsor: 
has dmc: No
The purpose of the trial is to investigate the efficacy of combining tolterodine and
      desmopressin compared with tolterodine monotherapy in the treatment of women with overactive
      bladder with nocturia in terms of reduction of nocturnal voids during 3 months of treatment
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in Mean Number of Nocturnal Voids From Baseline
time frame: Baseline to 3 months of treatment
description: A nocturnal void was defined as a void occurring at least 5 minutes after going to bed, but before getting up the next morning. The mean estimate was the average over 3 consecutive 24-hour periods prior to the respective visit as captured in the voiding and sleep diary.
measure: Change in Mean Time to First Nocturnal Void From Baseline
time frame: Baseline to 3 months of treatment
description: The time to first nocturnal void was defined as the time from going to bed with the intention of sleeping until first nocturnal void or until waking in the morning in the case there is no nocturnal void. The time to first void was calculated as the average over three consecutive 24-hour periods prior to the respective visits.
measure: Change in Mean Nocturnal Urine Volume From Baseline
time frame: Baseline to 3 months of treatment
description: The mean nocturnal urine volume was derived from the three-day urine volume diary. The nocturnal volume was defined as the sum of the volumes for all nocturnal voids including the volume of the first morning void within 30 min of waking up in the morning.
measure: Responder Status
time frame: Baseline to 3 months of treatment
description: Responder status was defined as ≥33% decrease in the mean number of nocturnal void and at least one night with no voids out of the 3-day diary period.
measure: Onset of Effect as Seen in Change in Mean Number of Nocturnal Voids From Baseline for Each Visit During Three Months of Treatment
time frame: Baseline to 3 months of treatment
description: A nocturnal void was defined as a void occurring at least 5 minutes after going to bed, but before getting up the next morning. The mean estimate was the average over 3 consecutive 24-hour periods prior to the respective visit as captured in the voiding and sleep diary.
measure: Change in the Impact on Sleep as Measured by the Sleep Rating Scales From Baseline
time frame: Baseline to 3 months of treatment
description: An electronic diary was used in the trial to document the impact on sleep quality (sleep rating scales). The sleep rating scales included three questions that ranged from 0 (poor) to 10 (good). The average of each question for each visit was summarised and the change from baseline was analysed longitudinally during the three months of treatment.
arm group label: Combination
arm group type: Experimental
description: Tolterodine tartrate extended release capsules + Desmopressin orally disintegrating tablets
arm group label: Tolterodine
arm group type: Active Comparator
description: Tolterodine tartrate extended release capsules + Placebo orally disintegrating tablets
intervention type: Drug
intervention name: Tolterodine tartrate extended release capsules
arm group label: Combination
arm group label: Tolterodine
intervention type: Drug
intervention name: Desmopressin orally disintegrating tablets
arm group label: Combination
intervention type: Drug
intervention name: Placebo orally disintegrating tablets
arm group label: Tolterodine
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Development Support
role: Study Director
affiliation: Ferring Pharmaceuticals
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country: United States
responsible party type: Sponsor
mesh term: Urinary Bladder, Overactive
mesh term: Nocturia
mesh term: Deamino Arginine Vasopressin
mesh term: Tolterodine Tartrate
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 