<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/NCT01707667</url>
  </required_header>
  <id_info>
    <org_study_id>SPD555-403</org_study_id>
    <secondary_id>2012-002495-13</secondary_id>
    <nct_id>NCT01707667</nct_id>
  </id_info>
  <brief_title>Study to Investigate Prucalopride vs. Polyethylene Glycol 3350 on Colon Activity</brief_title>
  <official_title>An Open-label, Randomized, Crossover, Reader-blinded Study to Investigate the Effect of Prucalopride and Polyethylene Glycol 3350 on Colon Motility With Intramural Manometry in Subjects With Chronic Constipation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shire</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Takeda</source>
  <brief_summary>
    <textblock>
      To evaluate the different effects of prucalopride and PEG 3350 + electrolytes on colon motor&#xD;
      activity in subjects that are chronically constipated.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 27, 2013</start_date>
  <completion_date type="Actual">November 27, 2013</completion_date>
  <primary_completion_date type="Actual">November 27, 2013</primary_completion_date>
  <phase>Phase 4</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The Number of High-Amplitude Propagating Contractions (HAPC)</measure>
    <time_frame>over 12 hours post-dose</time_frame>
    <description>Manometry recordings were read by an experienced gastroenterologist who was blinded to the treatment each subject received. The tracings were analyzed using computer-based validated software. HAPC and manometry data were available for every sensor as well as average values for each HAPC and manometry time point. The primary outcome analysis of HAPC data used the following threshold: Mean amplitude ≥100mmHg and extension ≥20cm (9 sensors).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area Under the Concentration Curve (AUC) of All HAPCs</measure>
    <time_frame>over 12 hours post-dose</time_frame>
    <description>The AUC of all HAPCs during the first 12 hours after treatment was calculated as the sum of the AUC at all sensors of each HAPC at the ≥100mmHg and ≥20cm threshold.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Mean Amplitude of HAPC</measure>
    <time_frame>over 12 hours post-dose</time_frame>
    <description>The mean amplitude of all HAPCs was calculated as the sum of the mean amplitude for each HAPC divided by the number of HAPCs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to First HAPC</measure>
    <time_frame>over 12 hours post-dose</time_frame>
    <description>The median (95% CI) time to first HAPC after administration of investigational product with amplitude ≥100mmHg and extension ≥20cm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Propagation Velocity of HAPC</measure>
    <time_frame>over 12 hours post-dose</time_frame>
    <description>Propagation velocity was calculated as the extension divided by the duration for each HAPC. Mean propagation velocity is the sum of the propagation velocities divided by the number of HAPCs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of HAPC</measure>
    <time_frame>over 12 hours post-dose</time_frame>
    <description>The mean duration of all HAPCs was calculated as the sum of the duration of each HAPC divided by the number of HAPCs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Motility Index</measure>
    <time_frame>over 12 hours post-dose</time_frame>
    <description>Motility index (mmHg) was summarized for the following 3 time points: pre-dose, 0-5 hours post-dose, and 5-12 hours post-dose. The motility index is defined as the natural logarithm of all peak amplitudes of every contraction +1.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Chronic Constipation</condition>
  <arm_group>
    <arm_group_label>Prucalopride</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>PEG 3350</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>prucalopride</intervention_name>
    <description>One 2 mg tablet orally administered on Day 1</description>
    <arm_group_label>Prucalopride</arm_group_label>
    <other_name>Resolor (Marketed name in Europe)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PEG 3350</intervention_name>
    <description>13.8g polyethylene glycol (PEG) 3350 with sodium bicarbonate, sodium chloride, and potassium chloride as a solution in water. Administered twice orally on Day 1(once in the morning and once prior to lunch).</description>
    <arm_group_label>PEG 3350</arm_group_label>
    <other_name>Movicol</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Chronic constipation&#xD;
&#xD;
          -  Male or female ages 18-75 years&#xD;
&#xD;
          -  Non-pregnant, non-lactating female&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Drug-induced constipation&#xD;
&#xD;
          -  Subjects suffering from secondary causes of chronic constipation, such as:&#xD;
&#xD;
          -  Endocrine disorders, e.g. hypopituitarism, hypothyroidism, hypercalcemia,&#xD;
             pseudohypoparathyroidism, pheochromocytoma or glucagon-producing tumors, unless these&#xD;
             are controlled by appropriate medical therapy.&#xD;
&#xD;
          -  Metabolic disorders, e.g. porphyria, uremia, hypokalemia or amyloid neuropathy, unless&#xD;
             these are controlled by appropriate medical therapy&#xD;
&#xD;
          -  Neurological disorders, e.g. Parkinson's disease, cerebral tumors, cerebrovascular&#xD;
             accidents, multiple sclerosis, meningocele, aganglionosis, hypoganglionosis,&#xD;
             hyperganglionosis, autonomic neuropathy or neuropathy due to chemotherapy, spinal cord&#xD;
             injury, Chaga's disease, or major depression&#xD;
&#xD;
          -  Surgery.&#xD;
&#xD;
          -  Subjects with insulin-dependent diabetes mellitus&#xD;
&#xD;
          -  Rectal evacuation disorder/outlet obstruction&#xD;
&#xD;
          -  Subjects with intestinal perforation or obstruction&#xD;
&#xD;
          -  Severe renal impairment&#xD;
&#xD;
          -  Subjects with a history of alcohol or drug abuse&#xD;
&#xD;
          -  Subjects with lactose intolerance&#xD;
&#xD;
          -  Subjects with clinically significant cardiac, vascular, liver, pulmonary, endocrine,&#xD;
             neurological or psychiatric disorders&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Takeda</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Oklahoma Foundation for Digestive Research</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UNIVERSITY OF LEUVEN, UNVERSITY HOSPITAL, Gasthuisberg</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Barts Health NHS Trust</name>
      <address>
        <city>Whitechapel</city>
        <state>London</state>
        <zip>E1 1BB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>October 12, 2012</study_first_submitted>
  <study_first_submitted_qc>October 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 16, 2012</study_first_posted>
  <results_first_submitted>October 17, 2014</results_first_submitted>
  <results_first_submitted_qc>October 17, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">October 22, 2014</results_first_posted>
  <last_update_submitted>June 10, 2021</last_update_submitted>
  <last_update_submitted_qc>June 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 2, 2021</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>Constipation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prucalopride</mesh_term>
    <mesh_term>Polyethylene glycol 3350</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>PRU-PEG</title>
          <description>A single dose of prucalopride 2mg in the first period followed by 2 doses of polyethylene glycol (PEG) 3350 (13.8g) plus electrolytes in the second period.</description>
        </group>
        <group group_id="P2">
          <title>PEG-PRU</title>
          <description>Two doses of PEG 3350 (13.8g) plus electrolytes in the first period followed by a single dose of prucalopride 2mg in the second period.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Period 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>expulsion of colonic sensor catheter</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Period 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The Safety Analysis Set consisted of all randomized subjects who had taken at least 1 dose of investigational product.</population>
      <group_list>
        <group group_id="B1">
          <title>PRU-PEG</title>
          <description>A single dose of prucalopride 2mg in the first period followed by 2 doses of polyethylene glycol (PEG) 3350 (13.8g) plus electrolytes in the second period.</description>
        </group>
        <group group_id="B2">
          <title>PEG-PRU</title>
          <description>Two doses of PEG 3350 (13.8g) plus electrolytes in the first period followed by a single dose of prucalopride 2mg in the second period.</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="7"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="13"/>
          </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="40.3" spread="11.04"/>
                    <measurement group_id="B2" value="35.2" spread="13.18"/>
                    <measurement group_id="B3" value="37.9" spread="11.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>18 - 64</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="13"/>
                  </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="7"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="13"/>
                  </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>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>UNITED STATES</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Number of High-Amplitude Propagating Contractions (HAPC)</title>
        <description>Manometry recordings were read by an experienced gastroenterologist who was blinded to the treatment each subject received. The tracings were analyzed using computer-based validated software. HAPC and manometry data were available for every sensor as well as average values for each HAPC and manometry time point. The primary outcome analysis of HAPC data used the following threshold: Mean amplitude ≥100mmHg and extension ≥20cm (9 sensors).</description>
        <time_frame>over 12 hours post-dose</time_frame>
        <population>The Pharmacodynamic Analysis Set consisted of all randomized subjects who had taken at least 1 dose of investigational product and who had 1 evaluable manometry assessment (minimum of 4 hours of manometry recordings from the intake of investigational product) for each treatment period.</population>
        <group_list>
          <group group_id="O1">
            <title>Prucalopride</title>
            <description>A single dose of 2mg prucalopride, administered orally as tablets with 125mL of water on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>PEG 3350</title>
            <description>13.8g polyethylene glycol (PEG) 3350 with sodium bicarbonate, sodium chloride, and potassium chloride as a solution in water. Administered twice orally on Day 1 (once in the morning and once prior to lunch).</description>
          </group>
        </group_list>
        <measure>
          <title>The Number of High-Amplitude Propagating Contractions (HAPC)</title>
          <description>Manometry recordings were read by an experienced gastroenterologist who was blinded to the treatment each subject received. The tracings were analyzed using computer-based validated software. HAPC and manometry data were available for every sensor as well as average values for each HAPC and manometry time point. The primary outcome analysis of HAPC data used the following threshold: Mean amplitude ≥100mmHg and extension ≥20cm (9 sensors).</description>
          <population>The Pharmacodynamic Analysis Set consisted of all randomized subjects who had taken at least 1 dose of investigational product and who had 1 evaluable manometry assessment (minimum of 4 hours of manometry recordings from the intake of investigational product) for each treatment period.</population>
          <units>Number of HAPC with amplitude ≥100mmHg</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.7" spread="2.06"/>
                    <measurement group_id="O2" value="2.9" spread="2.06"/>
                  </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>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.012</p_value>
            <method>Linear Mixed-Effect Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>5.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.6</ci_lower_limit>
            <ci_upper_limit>9.9</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Concentration Curve (AUC) of All HAPCs</title>
        <description>The AUC of all HAPCs during the first 12 hours after treatment was calculated as the sum of the AUC at all sensors of each HAPC at the ≥100mmHg and ≥20cm threshold.</description>
        <time_frame>over 12 hours post-dose</time_frame>
        <population>The Pharmacodynamic Analysis Set consisted of all randomized subjects who had taken at least 1 dose of investigational product and who had 1 evaluable manometry assessment (minimum of 4 hours of manometry recordings from the intake of investigational product) for each treatment period.</population>
        <group_list>
          <group group_id="O1">
            <title>Prucalopride</title>
            <description>A single dose of 2mg prucalopride, administered orally as tablets with 125mL of water on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>PEG 3350</title>
            <description>13.8g polyethylene glycol (PEG) 3350 with sodium bicarbonate, sodium chloride, and potassium chloride as a solution in water. Administered twice orally on Day 1 (once in the morning and once prior to lunch).</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration Curve (AUC) of All HAPCs</title>
          <description>The AUC of all HAPCs during the first 12 hours after treatment was calculated as the sum of the AUC at all sensors of each HAPC at the ≥100mmHg and ≥20cm threshold.</description>
          <population>The Pharmacodynamic Analysis Set consisted of all randomized subjects who had taken at least 1 dose of investigational product and who had 1 evaluable manometry assessment (minimum of 4 hours of manometry recordings from the intake of investigational product) for each treatment period.</population>
          <units>mmHg.sec</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="110204.1" spread="28279.91"/>
                    <measurement group_id="O2" value="41152.7" spread="34432.61"/>
                  </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>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.079</p_value>
            <method>Linear Mixed-Effect Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>69051.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-12004.5</ci_lower_limit>
            <ci_upper_limit>150107.3</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Mean Amplitude of HAPC</title>
        <description>The mean amplitude of all HAPCs was calculated as the sum of the mean amplitude for each HAPC divided by the number of HAPCs.</description>
        <time_frame>over 12 hours post-dose</time_frame>
        <population>The Pharmacodynamic Analysis Set consisted of all randomized subjects who had taken at least 1 dose of investigational product and who had 1 evaluable manometry assessment (minimum of 4 hours of manometry recordings from the intake of investigational product) for each treatment period.</population>
        <group_list>
          <group group_id="O1">
            <title>Prucalopride</title>
            <description>A single dose of 2mg prucalopride, administered orally as tablets with 125mL of water on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>PEG 3350</title>
            <description>13.8g polyethylene glycol (PEG) 3350 with sodium bicarbonate, sodium chloride, and potassium chloride as a solution in water. Administered twice orally on Day 1 (once in the morning and once prior to lunch).</description>
          </group>
        </group_list>
        <measure>
          <title>The Mean Amplitude of HAPC</title>
          <description>The mean amplitude of all HAPCs was calculated as the sum of the mean amplitude for each HAPC divided by the number of HAPCs.</description>
          <population>The Pharmacodynamic Analysis Set consisted of all randomized subjects who had taken at least 1 dose of investigational product and who had 1 evaluable manometry assessment (minimum of 4 hours of manometry recordings from the intake of investigational product) for each treatment period.</population>
          <units>mmHg</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="199.0" spread="15.15"/>
                    <measurement group_id="O2" value="189.8" spread="19.56"/>
                  </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>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.717</p_value>
            <method>Linear Mixed-Effect Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>9.2</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-45.3</ci_lower_limit>
            <ci_upper_limit>63.7</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to First HAPC</title>
        <description>The median (95% CI) time to first HAPC after administration of investigational product with amplitude ≥100mmHg and extension ≥20cm.</description>
        <time_frame>over 12 hours post-dose</time_frame>
        <population>The Pharmacodynamic Analysis Set included all subjects in the Safety Analysis Set who had 1 evaluable manometry assessment (minimum of 4 hours of manometry recordings from the intake of investigational product) for each treatment period.</population>
        <group_list>
          <group group_id="O1">
            <title>Prucalopride</title>
            <description>A single dose of 2mg prucalopride, administered orally as tablets with 125mL of water on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>PEG 3350</title>
            <description>13.8g polyethylene glycol (PEG) 3350 with sodium bicarbonate, sodium chloride, and potassium chloride as a solution in water. Administered twice orally on Day 1 (once in the morning and once prior to lunch).</description>
          </group>
        </group_list>
        <measure>
          <title>Time to First HAPC</title>
          <description>The median (95% CI) time to first HAPC after administration of investigational product with amplitude ≥100mmHg and extension ≥20cm.</description>
          <population>The Pharmacodynamic Analysis Set included all subjects in the Safety Analysis Set who had 1 evaluable manometry assessment (minimum of 4 hours of manometry recordings from the intake of investigational product) for each treatment period.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.5" lower_limit="1.5" upper_limit="9.3"/>
                    <measurement group_id="O2" value="NA" lower_limit="2.8" upper_limit="NA">The median time to first HAPC after administration of investigational product with amplitude ≥100mmHg and extension ≥20cm in the PEG 3350 group could not be calculated as only 6 subjects had HAPCs that met this threshold.</measurement>
                  </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>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.295</p_value>
            <method>Log Rank</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Propagation Velocity of HAPC</title>
        <description>Propagation velocity was calculated as the extension divided by the duration for each HAPC. Mean propagation velocity is the sum of the propagation velocities divided by the number of HAPCs.</description>
        <time_frame>over 12 hours post-dose</time_frame>
        <population>The Pharmacodynamic Analysis Set consisted of all randomized subjects who had taken at least 1 dose of investigational product and who had 1 evaluable manometry assessment (minimum of 4 hours of manometry recordings from the intake of investigational product) for each treatment period.</population>
        <group_list>
          <group group_id="O1">
            <title>Prucalopride</title>
            <description>A single dose of 2mg prucalopride, administered orally as tablets with 125mL of water on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>PEG 3350</title>
            <description>13.8g polyethylene glycol (PEG) 3350 with sodium bicarbonate, sodium chloride, and potassium chloride as a solution in water. Administered twice orally on Day 1 (once in the morning and once prior to lunch).</description>
          </group>
        </group_list>
        <measure>
          <title>Propagation Velocity of HAPC</title>
          <description>Propagation velocity was calculated as the extension divided by the duration for each HAPC. Mean propagation velocity is the sum of the propagation velocities divided by the number of HAPCs.</description>
          <population>The Pharmacodynamic Analysis Set consisted of all randomized subjects who had taken at least 1 dose of investigational product and who had 1 evaluable manometry assessment (minimum of 4 hours of manometry recordings from the intake of investigational product) for each treatment period.</population>
          <units>cm/sec</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.467" spread="0.0803"/>
                    <measurement group_id="O2" value="0.646" spread="0.1074"/>
                  </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>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.180</p_value>
            <method>Linear Mixed-Effect Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.179</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.465</ci_lower_limit>
            <ci_upper_limit>0.107</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of HAPC</title>
        <description>The mean duration of all HAPCs was calculated as the sum of the duration of each HAPC divided by the number of HAPCs.</description>
        <time_frame>over 12 hours post-dose</time_frame>
        <population>The Pharmacodynamic Analysis Set consisted of all randomized subjects who had taken at least 1 dose of investigational product and who had 1 evaluable manometry assessment (minimum of 4 hours of manometry recordings from the intake of investigational product) for each treatment period.</population>
        <group_list>
          <group group_id="O1">
            <title>Prucalopride</title>
            <description>A single dose of 2mg prucalopride, administered orally as tablets with 125mL of water on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>PEG 3350</title>
            <description>13.8g polyethylene glycol (PEG) 3350 with sodium bicarbonate, sodium chloride, and potassium chloride as a solution in water. Administered twice orally on Day 1 (once in the morning and once prior to lunch).</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of HAPC</title>
          <description>The mean duration of all HAPCs was calculated as the sum of the duration of each HAPC divided by the number of HAPCs.</description>
          <population>The Pharmacodynamic Analysis Set consisted of all randomized subjects who had taken at least 1 dose of investigational product and who had 1 evaluable manometry assessment (minimum of 4 hours of manometry recordings from the intake of investigational product) for each treatment period.</population>
          <units>sec</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="84.9" spread="8.05"/>
                    <measurement group_id="O2" value="69.1" spread="10.75"/>
                  </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>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.225</p_value>
            <method>Linear Mixed-Effect Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>15.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-12.6</ci_lower_limit>
            <ci_upper_limit>44.3</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Motility Index</title>
        <description>Motility index (mmHg) was summarized for the following 3 time points: pre-dose, 0-5 hours post-dose, and 5-12 hours post-dose. The motility index is defined as the natural logarithm of all peak amplitudes of every contraction +1.</description>
        <time_frame>over 12 hours post-dose</time_frame>
        <population>The Pharmacodynamic Analysis Set consisted of all randomized subjects who had taken at least 1 dose of investigational product and who had 1 evaluable manometry assessment (minimum of 4 hours of manometry recordings from the intake of investigational product) for each treatment period.</population>
        <group_list>
          <group group_id="O1">
            <title>Prucalopride</title>
            <description>A single dose of 2mg prucalopride, administered orally as tablets with 125mL of water on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>PEG 3350</title>
            <description>13.8g polyethylene glycol (PEG) 3350 with sodium bicarbonate, sodium chloride, and potassium chloride as a solution in water. Administered twice orally on Day 1 (once in the morning and once prior to lunch).</description>
          </group>
        </group_list>
        <measure>
          <title>Motility Index</title>
          <description>Motility index (mmHg) was summarized for the following 3 time points: pre-dose, 0-5 hours post-dose, and 5-12 hours post-dose. The motility index is defined as the natural logarithm of all peak amplitudes of every contraction +1.</description>
          <population>The Pharmacodynamic Analysis Set consisted of all randomized subjects who had taken at least 1 dose of investigational product and who had 1 evaluable manometry assessment (minimum of 4 hours of manometry recordings from the intake of investigational product) for each treatment period.</population>
          <units>mmHg</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pre-Dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.467" spread="0.4668"/>
                    <measurement group_id="O2" value="8.312" spread="0.4403"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>0-5 hours post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.661" spread="0.3221"/>
                    <measurement group_id="O2" value="13.349" spread="0.3520"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>5-12 hours post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.208" spread="0.2976"/>
                    <measurement group_id="O2" value="14.390" spread="0.2489"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Prucalopride</title>
          <description>A single dose of 2mg prucalopride, administered orally as tablets with 125mL of water on Day 1.</description>
        </group>
        <group group_id="E2">
          <title>Polyethylene Glycol</title>
          <description>13.8g polyethylene glycol (PEG) 3350 with sodium bicarbonate, sodium chloride, and potassium chloride as a solution in water. Administered twice orally on Day 1 (once in the morning and once prior to lunch).</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <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="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>ABDOMINAL PAIN</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>DIARRHOEA</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>NAUSEA</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>RECTAL HAEMORRHAGE</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>HEADACHE</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </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>If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Shire</organization>
      <phone>+1 866 842 5335</phone>
      <email>ClinicalTransparency@shire.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/NCT01707667
org study id: SPD555-403
secondary id: 2012-002495-13
nct id: NCT01707667
lead sponsor: 
To evaluate the different effects of prucalopride and PEG 3350 + electrolytes on colon motor
      activity in subjects that are chronically constipated.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The Number of High-Amplitude Propagating Contractions (HAPC)
time frame: over 12 hours post-dose
description: Manometry recordings were read by an experienced gastroenterologist who was blinded to the treatment each subject received. The tracings were analyzed using computer-based validated software. HAPC and manometry data were available for every sensor as well as average values for each HAPC and manometry time point. The primary outcome analysis of HAPC data used the following threshold: Mean amplitude ≥100mmHg and extension ≥20cm (9 sensors).
measure: Area Under the Concentration Curve (AUC) of All HAPCs
time frame: over 12 hours post-dose
description: The AUC of all HAPCs during the first 12 hours after treatment was calculated as the sum of the AUC at all sensors of each HAPC at the ≥100mmHg and ≥20cm threshold.
measure: The Mean Amplitude of HAPC
time frame: over 12 hours post-dose
description: The mean amplitude of all HAPCs was calculated as the sum of the mean amplitude for each HAPC divided by the number of HAPCs.
measure: Time to First HAPC
time frame: over 12 hours post-dose
description: The median (95% CI) time to first HAPC after administration of investigational product with amplitude ≥100mmHg and extension ≥20cm.
measure: Propagation Velocity of HAPC
time frame: over 12 hours post-dose
description: Propagation velocity was calculated as the extension divided by the duration for each HAPC. Mean propagation velocity is the sum of the propagation velocities divided by the number of HAPCs.
measure: Duration of HAPC
time frame: over 12 hours post-dose
description: The mean duration of all HAPCs was calculated as the sum of the duration of each HAPC divided by the number of HAPCs.
measure: Motility Index
time frame: over 12 hours post-dose
description: Motility index (mmHg) was summarized for the following 3 time points: pre-dose, 0-5 hours post-dose, and 5-12 hours post-dose. The motility index is defined as the natural logarithm of all peak amplitudes of every contraction +1.
arm group label: Prucalopride
arm group type: Experimental
arm group label: PEG 3350
arm group type: Active Comparator
intervention type: Drug
intervention name: prucalopride
description: One 2 mg tablet orally administered on Day 1
arm group label: Prucalopride
other name: Resolor (Marketed name in Europe)
intervention type: Drug
intervention name: PEG 3350
description: 13.8g polyethylene glycol (PEG) 3350 with sodium bicarbonate, sodium chloride, and potassium chloride as a solution in water. Administered twice orally on Day 1(once in the morning and once prior to lunch).
arm group label: PEG 3350
other name: Movicol
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Study Director
role: Study Director
affiliation: Takeda
facility: 
facility: 
facility: 
country: Belgium
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Constipation
mesh term: Prucalopride
mesh term: Polyethylene glycol 3350
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 