<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/NCT01722318</url>
  </required_header>
  <id_info>
    <org_study_id>SP304-20212</org_study_id>
    <nct_id>NCT01722318</nct_id>
  </id_info>
  <brief_title>The Plecanatide Irritable Bowel Syndrome With Constipation Study (IBS-C)</brief_title>
  <acronym>CIBS</acronym>
  <official_title>A Randomized, 12-Week, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Assess the Safety and Efficacy of Plecanatide in Patients With Irritable Bowel Syndrome With Constipation (IBS-C)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bausch Health Americas, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Bausch Health Americas, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized, 12-week, double-blind, placebo-controlled, dose-ranging study in&#xD;
      patients with IBS-C.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, 12-week, double-blind, placebo-controlled, dose-ranging study in&#xD;
      patients with IBS-C. Patients will undergo a Screening Period to determine eligibility. After&#xD;
      completing a Screening Visit patients will undergo a 2-week Pre-Treatment assessment using&#xD;
      the Interactive Voice Response System (IVRS) during which they will complete daily&#xD;
      assessments of bowel movements (BMs), stool consistency (Bristol Stool Form Scale- BSFS),&#xD;
      abdominal pain or abdominal discomfort and other symptoms associated with IBS-C. Data from&#xD;
      the two-week IVRS Pre-treatment assessment are used to define the patient's baseline from&#xD;
      which change will be determined. Patients who meet all entry criteria will be randomized to&#xD;
      one of five treatment groups ( 0.3mg,1.0mg,3.0mg,9mg,or Placebo) on Day 1 of the Treatment&#xD;
      Period. Patients will take an oral dose of study drug daily (QD) for 12 weeks and continue&#xD;
      the daily IVRS diaries (BMs, abdominal pain, other symptoms). On Weeks 2, 4, 8, and 12,&#xD;
      patients will return to the clinic to undergo safety and efficacy assessments. For 2 weeks&#xD;
      after completing dosing, (i.e., Post-Treatment Period), patients will continue to complete&#xD;
      daily IVRS diaries. Patients will then return to the clinical site for a final follow-up&#xD;
      visit (End of Study Visit). The planned duration of participation in this study will be&#xD;
      approximately 112 days from signing of informed consent through post-treatment or 145 days if&#xD;
      30 day washout of a prohibited concomitant medication or stabilization of a medical condition&#xD;
      is required before Pre-Treatment (up to 148 days, with all windows considered).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">October 2014</completion_date>
  <primary_completion_date type="Actual">April 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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Weekly CSBMs Frequency Over the 12-Week Treatment Period (mITT Population)</measure>
    <time_frame>12 weeks Treatment Period</time_frame>
    <description>The primary efficacy endpoint was the change from baseline in the weekly CSBM frequency (CSBMs per week minus CSBMs per week at baseline) over a 12-week Treatment Period. A Complete Spontaneous Bowel Movement (CSBM) is a Bowel Movement (BM) that occurs in the absence of laxative use within 24 hours of the BM and the patient reports a feeling of complete evacuation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Abdominal Pain Intensity Scores Over 12-Week Treatment Period (mITT Population)</measure>
    <time_frame>12-Week Treatment Period</time_frame>
    <description>Abdominal Pain was assessed in the patient's daily response on a scale of 0 to 10 where 0 is did not experience the symptom at all and 10 is experienced the worst.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Stool Consistency (BSFS) Over 12-Week Treatment Period (mITT Population)</measure>
    <time_frame>12-Week Treatment Period</time_frame>
    <description>The stool consistency of each bowel movement (BM) was assessed by patients using the 7-point Bristol Stool Form Scale [BSFS] from 1 to 7.&#xD;
= separate hard lumps like nuts (difficult to pass)&#xD;
= sausage shaped but lumpy&#xD;
= like a sausage but with cracks on its surface&#xD;
= like a sausage or snake, smooth and soft&#xD;
= soft blobs with clear-cut edges (passed easily)&#xD;
= fluffy pieces with ragged edges, a mushy stool&#xD;
= watery, no solid pieces (entirely liquid)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Straining Scores Over 12-Week Treatment Period (mITT Population)</measure>
    <time_frame>12-Week Treatment Period</time_frame>
    <description>The severity of straining (Straining Score) was rated by the patients using a 11-point scale (0-10) where 0 = none and 10 = very severe</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">428</enrollment>
  <condition>Irritable Bowel Syndrome Characterized by Constipation</condition>
  <arm_group>
    <arm_group_label>Plecanatide 0.3mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Plecanatide 0.3mg, one tablet by mouth daily for 12 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Plecanatide 1.0mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Plecanatide 1.0mg one tablet by mouth daily for 12 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Plecanatide 3.0mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Plecanatide 3.0mg, one tablet by mouth daily for 12 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Plecanatide 9.0mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Plecanatide 9.0mg, one tablet by mouth daily for 12 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo, one tablet by mouth daily for 12 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Plecanatide</intervention_name>
    <arm_group_label>Plecanatide 0.3mg</arm_group_label>
    <arm_group_label>Plecanatide 1.0mg</arm_group_label>
    <arm_group_label>Plecanatide 3.0mg</arm_group_label>
    <arm_group_label>Plecanatide 9.0mg</arm_group_label>
    <other_name>Trulance</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female aged 18-75, inclusive&#xD;
&#xD;
          -  Body Mass Index = 18-35 kg/m2, inclusive&#xD;
&#xD;
          -  Meets modified Rome III criteria for irritable bowel syndrome with constipation which&#xD;
             includes abdominal pain or discomfort for at least 3 days/month in the last 3 months&#xD;
             with symptom onset for at least 6 months.&#xD;
&#xD;
          -  Less than 3 CSBMs and less than 6 SBMs per week during the last 3 months.&#xD;
&#xD;
          -  Hard or lumpy stools ≥ 25 % of defecations&#xD;
&#xD;
          -  Patient has average abdominal pain intensity scores ≥ 3 (scale 0-10)for the combined 2&#xD;
             week pre-treatment period&#xD;
&#xD;
          -  Patient is willing to discontinue use of supplemental fiber, laxatives, prescription&#xD;
             and nonprescription medications, herbal or dietary supplements intended to treat&#xD;
             constipation during the screening, pre-treatment, treatment and 2-week post-treatment&#xD;
             periods&#xD;
&#xD;
          -  Willing to maintain a stable diet during the study.&#xD;
&#xD;
          -  Patients with hemorrhoids and/or diverticulosis (NOT diverticulitis) CAN be entered&#xD;
             into the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Loose stool (mushy) or watery stool in the absence of any laxative or prohibited&#xD;
             medicine for &gt; 25% of BMs during the 3 months prior to screening visit OR during the&#xD;
             14 day pre-treatment period&#xD;
&#xD;
          -  Patient has diarrhea-predominant or mixed ( diarrhea and constipation cycling or&#xD;
             diarrhea and normal cycling) IBS.&#xD;
&#xD;
          -  Active peptic ulcer disease not adequately treated or not stable&#xD;
&#xD;
          -  History of cathartic colon, laxative, enema abuse, or ischemic colitis.&#xD;
&#xD;
          -  Fecal impaction within 3 months of screening&#xD;
&#xD;
          -  Patient has had /has any: structural abnormality of the GI tract or gastric bypass&#xD;
             surgery, pelvic floor dysfunction, pseudo-obstruction, active infectious gastritis,&#xD;
             diverticulitis, anal fissures or any disease or condition that can affect GI motility&#xD;
             or defecation or can be associated with abdominal pain&#xD;
&#xD;
          -  Unexplained and clinically significant &quot;alarm symptoms&quot; including lower GI bleeding,&#xD;
             iron-deficiency anemia, weight loss or systemic signs of infection or colitis.&#xD;
&#xD;
          -  Major surgery within 60 days of screening.&#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>Philip B Miner, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Oklahoma Foundation for Digestive Research</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cahaba Research</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Digestive Health Specialists of the Southeast</name>
      <address>
        <city>Dothan</city>
        <state>Alabama</state>
        <zip>36305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arrowhead Family Health Center PC dba Arrowhead Health Centers</name>
      <address>
        <city>Glendale</city>
        <state>Arizona</state>
        <zip>85306</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced Research Associates, LLC</name>
      <address>
        <city>Glendale</city>
        <state>Arizona</state>
        <zip>85308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Elite Clinical Trials, LLC</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85018</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Genova Clinical Research, Inc.</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Adobe Clinical Research, LLC</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85712</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lynn Institute of the Ozarks</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Anaheim Clinical Trials, LLC</name>
      <address>
        <city>Anaheim</city>
        <state>California</state>
        <zip>92801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced Rx Clinical Research, Inc.</name>
      <address>
        <city>Artesia</city>
        <state>California</state>
        <zip>90701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GW Research, Inc.</name>
      <address>
        <city>Chula Vista</city>
        <state>California</state>
        <zip>91910</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SC Clinical Research, Inc.</name>
      <address>
        <city>Garden Grove</city>
        <state>California</state>
        <zip>92844</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Grossmont Center for Clinical Research</name>
      <address>
        <city>La Mesa</city>
        <state>California</state>
        <zip>91942</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Community Clinical Trials</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Healthcare Partners Medical Group</name>
      <address>
        <city>Pasadena</city>
        <state>California</state>
        <zip>91105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Center for Clinical Research</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Research Medical Clinic d/b/a Orange Country Research Center</name>
      <address>
        <city>Tustin</city>
        <state>California</state>
        <zip>92780</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lynn Institute of the Rockies</name>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <zip>80907</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Horizons Clinical Research Center, LLC</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80220</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Consultants for Clinical Research of South Florida</name>
      <address>
        <city>Boynton Beach</city>
        <state>Florida</state>
        <zip>33426</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Research Unlimited, LLC</name>
      <address>
        <city>Hialeah</city>
        <state>Florida</state>
        <zip>33012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eastern Research, Inc</name>
      <address>
        <city>Hialeah</city>
        <state>Florida</state>
        <zip>33013</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Health Awareness, Inc.</name>
      <address>
        <city>Jupiter</city>
        <state>Florida</state>
        <zip>33458</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jupiter Research, Inc.</name>
      <address>
        <city>Jupiter</city>
        <state>Florida</state>
        <zip>33458</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MNH Surgical Center</name>
      <address>
        <city>Maitland</city>
        <state>Florida</state>
        <zip>32751</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>San Marcus Research Clinic, Inc.</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33015</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Genoma Research Group, Inc.</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33165</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbus Clinical Services, LLC</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33174</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>South Medical Research Group, Inc.</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33186</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Compass Research, LLC</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Urology Center of Florida</name>
      <address>
        <city>Pompano Beach</city>
        <state>Florida</state>
        <zip>33060</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Accord Clinical Research, LLC</name>
      <address>
        <city>Port Orange</city>
        <state>Florida</state>
        <zip>32129</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Meridien Research</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Palm Beach Research Center</name>
      <address>
        <city>West Palm Beach</city>
        <state>Florida</state>
        <zip>33409</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research of Central Florida</name>
      <address>
        <city>Winter Haven</city>
        <state>Florida</state>
        <zip>33880</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Georgia Regents University</name>
      <address>
        <city>Augusta</city>
        <state>Georgia</state>
        <zip>30912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Vernon Clinical Research, LLC</name>
      <address>
        <city>Sandy Springs</city>
        <state>Georgia</state>
        <zip>30328</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CTL Research</name>
      <address>
        <city>Eagle</city>
        <state>Idaho</state>
        <zip>83616</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medex Healthcare Research, Inc</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60602</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rockford Gastroenterology Associates</name>
      <address>
        <city>Rockford</city>
        <state>Illinois</state>
        <zip>61107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Heartland Research Associates, LLC</name>
      <address>
        <city>Augusta</city>
        <state>Kansas</state>
        <zip>67010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Integrity, LLC</name>
      <address>
        <city>Owensboro</city>
        <state>Kentucky</state>
        <zip>42303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Delta Research Partners, LLC</name>
      <address>
        <city>Bastrop</city>
        <state>Louisiana</state>
        <zip>71220</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gastroenterology Research of New Orleans</name>
      <address>
        <city>Hammond</city>
        <state>Louisiana</state>
        <zip>70403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centex Studies, Inc.</name>
      <address>
        <city>Lake Charles</city>
        <state>Louisiana</state>
        <zip>70601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women Under Study, LLC</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Louisiana Research Center, LLC</name>
      <address>
        <city>Shreveport</city>
        <state>Louisiana</state>
        <zip>71103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MGG Group Co., Inc., Chevy Chase Clinical Research</name>
      <address>
        <city>Chevy Chase</city>
        <state>Maryland</state>
        <zip>20815</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boston Clinical Trials</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02131</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novex Clinical Research, LLC</name>
      <address>
        <city>New Bedford</city>
        <state>Massachusetts</state>
        <zip>02740</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bay State Clinical Trials, Inc.</name>
      <address>
        <city>Watertown</city>
        <state>Massachusetts</state>
        <zip>02472</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IHA Chelsea Family &amp; Internal Medicine</name>
      <address>
        <city>Chelsea</city>
        <state>Michigan</state>
        <zip>48118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research Institute of Michigan, LLC</name>
      <address>
        <city>Chesterfield</city>
        <state>Michigan</state>
        <zip>48047</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center for Digestive Health</name>
      <address>
        <city>Troy</city>
        <state>Michigan</state>
        <zip>48098</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ridgeview Research</name>
      <address>
        <city>Chaska</city>
        <state>Minnesota</state>
        <zip>55318</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prism Research</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Center for Clinical Trials</name>
      <address>
        <city>Biloxi</city>
        <state>Mississippi</state>
        <zip>39531</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gastrointestinal Associates, PA</name>
      <address>
        <city>Jackson</city>
        <state>Mississippi</state>
        <zip>39202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Louis Center for Clinical Research</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63128</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montana Health Research Institute, Inc.</name>
      <address>
        <city>Billings</city>
        <state>Montana</state>
        <zip>59102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Internal Medical Associates of Grand Island, PC</name>
      <address>
        <city>Grand Island</city>
        <state>Nebraska</state>
        <zip>68803</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Quality Clinical Research, Inc.</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dartmouth-Hitchcock Medical Center</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Luke's Hospital</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10025</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asheville Gastroenterology Associates, PA</name>
      <address>
        <city>Asheville</city>
        <state>North Carolina</state>
        <zip>28801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MediSpect Medical Research, LLC</name>
      <address>
        <city>Boone</city>
        <state>North Carolina</state>
        <zip>28607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trials of North Carolina, LLC</name>
      <address>
        <city>Cary</city>
        <state>North Carolina</state>
        <zip>27518</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carolina Digestive Health Associates</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>On Site Clinical, LLC</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28277</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carolina Digestive Health Associates</name>
      <address>
        <city>Davidson</city>
        <state>North Carolina</state>
        <zip>28036</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cumberland Research Associates, LLC</name>
      <address>
        <city>Fayetteville</city>
        <state>North Carolina</state>
        <zip>28304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LeBauer Research Associates, P.A.</name>
      <address>
        <city>Greensboro</city>
        <state>North Carolina</state>
        <zip>27403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medoff Medical / Vital re:Search</name>
      <address>
        <city>Greensboro</city>
        <state>North Carolina</state>
        <zip>27408</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wake Research Associates, LLC</name>
      <address>
        <city>Raleigh</city>
        <state>North Carolina</state>
        <zip>27612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PMG Research of Winston-Salem, LLC</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hometown Urgent Care and Occupational Health</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43214</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Great Lakes Gastroenterology</name>
      <address>
        <city>Mentor</city>
        <state>Ohio</state>
        <zip>44060</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Sooner Research</name>
      <address>
        <city>Norman</city>
        <state>Oklahoma</state>
        <zip>73071</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <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>Lynn Health Science Institute</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Options Health Research, LLC</name>
      <address>
        <city>Tulsa</city>
        <state>Oklahoma</state>
        <zip>74104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Consultants in Gastroenterology</name>
      <address>
        <city>Columbia</city>
        <state>South Carolina</state>
        <zip>29203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southeast Medical Research</name>
      <address>
        <city>North Charleston</city>
        <state>South Carolina</state>
        <zip>29406</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Palmetto Clinical Research</name>
      <address>
        <city>Summerville</city>
        <state>South Carolina</state>
        <zip>29485</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chattanooga Medical Research LLC</name>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <zip>37404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ClinSearch, LLC</name>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <zip>37421</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Franklin Gastroenterology, PLLC</name>
      <address>
        <city>Franklin</city>
        <state>Tennessee</state>
        <zip>37067</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memphis Gastroenterology Group, PC</name>
      <address>
        <city>Germantown</city>
        <state>Tennessee</state>
        <zip>38138</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Associates in Gastroenterology</name>
      <address>
        <city>Hermitage</city>
        <state>Tennessee</state>
        <zip>37076</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Austin Center for Clinical Research</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>DCT-AACT, LLC dba Discovery Clinical Trials</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78758</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Tech Medical Center</name>
      <address>
        <city>El Paso</city>
        <state>Texas</state>
        <zip>79905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centex Studies, Inc.</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77062</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Texas Family Medicine</name>
      <address>
        <city>Plano</city>
        <state>Texas</state>
        <zip>75093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Quality Research, Inc.</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Physician PrimeCare Research Institute, PLLC dba Health Texas Research Institute</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78228</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pioneer Research Solutions, Inc.</name>
      <address>
        <city>Sugar Land</city>
        <state>Texas</state>
        <zip>77479</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New River Valley Research Institute</name>
      <address>
        <city>Christiansburg</city>
        <state>Virginia</state>
        <zip>24073</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Blue Ridge Medical Research/Gastroenterology Associates of Central Virginia</name>
      <address>
        <city>Lynchburg</city>
        <state>Virginia</state>
        <zip>24502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>November 2, 2012</study_first_submitted>
  <study_first_submitted_qc>November 5, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 6, 2012</study_first_posted>
  <results_first_submitted>April 26, 2018</results_first_submitted>
  <results_first_submitted_qc>September 13, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">September 17, 2018</results_first_posted>
  <last_update_submitted>May 23, 2019</last_update_submitted>
  <last_update_submitted_qc>May 23, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 28, 2019</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>Irritable Bowel Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
    <mesh_term>Constipation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Plecanatide</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>The Enrollment number in the Protocol Section was changed from 350 to 428 participants to reflect the actual enrollment number.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Plecanatide 0.3mg</title>
          <description>Plecanatide 0.3mg, one tablet by mouth daily for 12 weeks&#xD;
Plecanatide</description>
        </group>
        <group group_id="P2">
          <title>Plecanatide 1.0mg</title>
          <description>Plecanatide 1.0mg one tablet by mouth daily for 12 weeks&#xD;
Plecanatide</description>
        </group>
        <group group_id="P3">
          <title>Plecanatide 3.0mg</title>
          <description>Plecanatide 3.0mg, one tablet by mouth daily for 12 weeks&#xD;
Plecanatide</description>
        </group>
        <group group_id="P4">
          <title>Plecanatide 9.0mg</title>
          <description>Plecanatide 9.0mg, one tablet by mouth daily for 12 weeks&#xD;
Plecanatide</description>
        </group>
        <group group_id="P5">
          <title>Placebo</title>
          <description>Placebo, one tablet by mouth daily for 12 weeks&#xD;
Placebo</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="86"/>
                <participants group_id="P2" count="85"/>
                <participants group_id="P3" count="86"/>
                <participants group_id="P4" count="85"/>
                <participants group_id="P5" count="86"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="72"/>
                <participants group_id="P2" count="65"/>
                <participants group_id="P3" count="66"/>
                <participants group_id="P4" count="65"/>
                <participants group_id="P5" count="68"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="20"/>
                <participants group_id="P3" count="20"/>
                <participants group_id="P4" count="20"/>
                <participants group_id="P5" count="18"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The Randomized Population (428 patients) in Participant Flow differs from the mITT Population (423 patients) because 1 patient was randomized and not dosed, 1 patient was dosed but had no post-baseline efficacy assessments, and 3 duplicate patient records (2 patients who were seen at 2 sites and 1 patient who was seen at 3 sites)</population>
      <group_list>
        <group group_id="B1">
          <title>Plecanatide 0.3mg</title>
          <description>Plecanatide 0.3mg, one tablet by mouth daily for 12 weeks&#xD;
Plecanatide</description>
        </group>
        <group group_id="B2">
          <title>Plecanatide 1.0mg</title>
          <description>Plecanatide 1.0mg one tablet by mouth daily for 12 weeks&#xD;
Plecanatide</description>
        </group>
        <group group_id="B3">
          <title>Plecanatide 3.0mg</title>
          <description>Plecanatide 3.0mg, one tablet by mouth daily for 12 weeks&#xD;
Plecanatide</description>
        </group>
        <group group_id="B4">
          <title>Plecanatide 9.0mg</title>
          <description>Plecanatide 9.0mg, one tablet by mouth daily for 12 weeks&#xD;
Plecanatide</description>
        </group>
        <group group_id="B5">
          <title>Placebo</title>
          <description>Placebo, one tablet by mouth daily for 12 weeks&#xD;
Placebo</description>
        </group>
        <group group_id="B6">
          <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="84"/>
            <count group_id="B2" value="83"/>
            <count group_id="B3" value="86"/>
            <count group_id="B4" value="85"/>
            <count group_id="B5" value="85"/>
            <count group_id="B6" value="423"/>
          </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="47.2" spread="12.02"/>
                    <measurement group_id="B2" value="44.6" spread="12.58"/>
                    <measurement group_id="B3" value="47.2" spread="12.89"/>
                    <measurement group_id="B4" value="45.3" spread="12.00"/>
                    <measurement group_id="B5" value="45.4" spread="12.02"/>
                    <measurement group_id="B6" value="45.9" spread="12.30"/>
                  </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="68"/>
                    <measurement group_id="B2" value="67"/>
                    <measurement group_id="B3" value="70"/>
                    <measurement group_id="B4" value="70"/>
                    <measurement group_id="B5" value="69"/>
                    <measurement group_id="B6" value="344"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="16"/>
                    <measurement group_id="B4" value="15"/>
                    <measurement group_id="B5" value="16"/>
                    <measurement group_id="B6" value="79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Weekly CSBMs Frequency Over the 12-Week Treatment Period (mITT Population)</title>
        <description>The primary efficacy endpoint was the change from baseline in the weekly CSBM frequency (CSBMs per week minus CSBMs per week at baseline) over a 12-week Treatment Period. A Complete Spontaneous Bowel Movement (CSBM) is a Bowel Movement (BM) that occurs in the absence of laxative use within 24 hours of the BM and the patient reports a feeling of complete evacuation.</description>
        <time_frame>12 weeks Treatment Period</time_frame>
        <population>The Modified Intent-to-Treat (mITT) population included all randomized patients who received ≥ 1 dose of study drug and ≥ 1 post-baseline BM assessment was the primary analysis population analyzed for efficacy endpoints.</population>
        <group_list>
          <group group_id="O1">
            <title>Plecanatide 0.3mg</title>
            <description>Plecanatide 0.3mg, one tablet by mouth daily for 12 weeks</description>
          </group>
          <group group_id="O2">
            <title>Plecanatide 1.0mg</title>
            <description>Plecanatide 1.0mg one tablet by mouth daily for 12 weeks</description>
          </group>
          <group group_id="O3">
            <title>Plecanatide 3.0mg</title>
            <description>Plecanatide 3.0mg, one tablet by mouth daily for 12 weeks</description>
          </group>
          <group group_id="O4">
            <title>Plecanatide 9.0mg</title>
            <description>Plecanatide 9.0mg, one tablet by mouth daily for 12 weeks</description>
          </group>
          <group group_id="O5">
            <title>Placebo</title>
            <description>Placebo, one tablet by mouth daily for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Weekly CSBMs Frequency Over the 12-Week Treatment Period (mITT Population)</title>
          <description>The primary efficacy endpoint was the change from baseline in the weekly CSBM frequency (CSBMs per week minus CSBMs per week at baseline) over a 12-week Treatment Period. A Complete Spontaneous Bowel Movement (CSBM) is a Bowel Movement (BM) that occurs in the absence of laxative use within 24 hours of the BM and the patient reports a feeling of complete evacuation.</description>
          <population>The Modified Intent-to-Treat (mITT) population included all randomized patients who received ≥ 1 dose of study drug and ≥ 1 post-baseline BM assessment was the primary analysis population analyzed for efficacy endpoints.</population>
          <units>CSBMs per week</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="84"/>
                <count group_id="O2" value="83"/>
                <count group_id="O3" value="86"/>
                <count group_id="O4" value="85"/>
                <count group_id="O5" value="85"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.28" spread="0.260"/>
                    <measurement group_id="O2" value="2.12" spread="0.265"/>
                    <measurement group_id="O3" value="2.74" spread="0.260"/>
                    <measurement group_id="O4" value="2.44" spread="0.262"/>
                    <measurement group_id="O5" value="1.27" spread="0.260"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Abdominal Pain Intensity Scores Over 12-Week Treatment Period (mITT Population)</title>
        <description>Abdominal Pain was assessed in the patient's daily response on a scale of 0 to 10 where 0 is did not experience the symptom at all and 10 is experienced the worst.</description>
        <time_frame>12-Week Treatment Period</time_frame>
        <population>The mITT population included all randomized patients who received at least 1 dose of study drug and who had at least 1 post-baseline Bowel Movement (BM) assessment was the primary analysis population for efficacy endpoints.</population>
        <group_list>
          <group group_id="O1">
            <title>Plecanatide 0.3mg</title>
            <description>Plecanatide 0.3mg, one tablet by mouth daily for 12 weeks</description>
          </group>
          <group group_id="O2">
            <title>Plecanatide 1.0mg</title>
            <description>Plecanatide 1.0mg one tablet by mouth daily for 12 weeks</description>
          </group>
          <group group_id="O3">
            <title>Plecanatide 3.0mg</title>
            <description>Plecanatide 3.0mg, one tablet by mouth daily for 12 weeks</description>
          </group>
          <group group_id="O4">
            <title>Plecanatide 9.0mg</title>
            <description>Plecanatide 9.0mg, one tablet by mouth daily for 12 weeks</description>
          </group>
          <group group_id="O5">
            <title>Placebo</title>
            <description>Placebo, one tablet by mouth daily for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Abdominal Pain Intensity Scores Over 12-Week Treatment Period (mITT Population)</title>
          <description>Abdominal Pain was assessed in the patient's daily response on a scale of 0 to 10 where 0 is did not experience the symptom at all and 10 is experienced the worst.</description>
          <population>The mITT population included all randomized patients who received at least 1 dose of study drug and who had at least 1 post-baseline Bowel Movement (BM) assessment was the primary analysis population for efficacy endpoints.</population>
          <units>scores on a scale</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="84"/>
                <count group_id="O2" value="83"/>
                <count group_id="O3" value="86"/>
                <count group_id="O4" value="85"/>
                <count group_id="O5" value="85"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.5" spread="0.20"/>
                    <measurement group_id="O2" value="-1.5" spread="0.20"/>
                    <measurement group_id="O3" value="-2.0" spread="0.20"/>
                    <measurement group_id="O4" value="-1.8" spread="0.20"/>
                    <measurement group_id="O5" value="-1.4" spread="0.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Stool Consistency (BSFS) Over 12-Week Treatment Period (mITT Population)</title>
        <description>The stool consistency of each bowel movement (BM) was assessed by patients using the 7-point Bristol Stool Form Scale [BSFS] from 1 to 7.&#xD;
= separate hard lumps like nuts (difficult to pass)&#xD;
= sausage shaped but lumpy&#xD;
= like a sausage but with cracks on its surface&#xD;
= like a sausage or snake, smooth and soft&#xD;
= soft blobs with clear-cut edges (passed easily)&#xD;
= fluffy pieces with ragged edges, a mushy stool&#xD;
= watery, no solid pieces (entirely liquid)</description>
        <time_frame>12-Week Treatment Period</time_frame>
        <population>The Modified Intent-to-Treat (mITT) population included all randomized patients who received ≥ 1 dose of study drug and ≥ 1 post-baseline BM assessment was the primary analysis population analyzed for efficacy endpoints.</population>
        <group_list>
          <group group_id="O1">
            <title>Plecanatide 0.3mg</title>
            <description>Plecanatide 0.3mg, one tablet by mouth daily for 12 weeks</description>
          </group>
          <group group_id="O2">
            <title>Plecanatide 1.0mg</title>
            <description>Plecanatide 1.0mg one tablet by mouth daily for 12 weeks</description>
          </group>
          <group group_id="O3">
            <title>Plecanatide 3.0mg</title>
            <description>Plecanatide 3.0mg, one tablet by mouth daily for 12 weeks</description>
          </group>
          <group group_id="O4">
            <title>Plecanatide 9.0mg</title>
            <description>Plecanatide 9.0mg, one tablet by mouth daily for 12 weeks</description>
          </group>
          <group group_id="O5">
            <title>Placebo</title>
            <description>Placebo, one tablet by mouth daily for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Stool Consistency (BSFS) Over 12-Week Treatment Period (mITT Population)</title>
          <description>The stool consistency of each bowel movement (BM) was assessed by patients using the 7-point Bristol Stool Form Scale [BSFS] from 1 to 7.&#xD;
= separate hard lumps like nuts (difficult to pass)&#xD;
= sausage shaped but lumpy&#xD;
= like a sausage but with cracks on its surface&#xD;
= like a sausage or snake, smooth and soft&#xD;
= soft blobs with clear-cut edges (passed easily)&#xD;
= fluffy pieces with ragged edges, a mushy stool&#xD;
= watery, no solid pieces (entirely liquid)</description>
          <population>The Modified Intent-to-Treat (mITT) population included all randomized patients who received ≥ 1 dose of study drug and ≥ 1 post-baseline BM assessment was the primary analysis population analyzed for efficacy endpoints.</population>
          <units>scores on a scale</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="84"/>
                <count group_id="O2" value="83"/>
                <count group_id="O3" value="86"/>
                <count group_id="O4" value="85"/>
                <count group_id="O5" value="85"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.63" spread="0.143"/>
                    <measurement group_id="O2" value="1.81" spread="0.144"/>
                    <measurement group_id="O3" value="2.49" spread="0.143"/>
                    <measurement group_id="O4" value="2.24" spread="0.145"/>
                    <measurement group_id="O5" value="1.01" spread="0.143"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Straining Scores Over 12-Week Treatment Period (mITT Population)</title>
        <description>The severity of straining (Straining Score) was rated by the patients using a 11-point scale (0-10) where 0 = none and 10 = very severe</description>
        <time_frame>12-Week Treatment Period</time_frame>
        <population>The Modified Intent-to-Treat (mITT) population included all randomized patients who received ≥ 1 dose of study drug and ≥ 1 post-baseline BM assessment was the primary analysis population analyzed for efficacy endpoints.</population>
        <group_list>
          <group group_id="O1">
            <title>Plecanatide 0.3mg</title>
            <description>Plecanatide 0.3mg, one tablet by mouth daily for 12 weeks</description>
          </group>
          <group group_id="O2">
            <title>Plecanatide 1.0mg</title>
            <description>Plecanatide 1.0mg one tablet by mouth daily for 12 weeks</description>
          </group>
          <group group_id="O3">
            <title>Plecanatide 3.0mg</title>
            <description>Plecanatide 3.0mg, one tablet by mouth daily for 12 weeks</description>
          </group>
          <group group_id="O4">
            <title>Plecanatide 9.0mg</title>
            <description>Plecanatide 9.0mg, one tablet by mouth daily for 12 weeks</description>
          </group>
          <group group_id="O5">
            <title>Placebo</title>
            <description>Placebo, one tablet by mouth daily for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Straining Scores Over 12-Week Treatment Period (mITT Population)</title>
          <description>The severity of straining (Straining Score) was rated by the patients using a 11-point scale (0-10) where 0 = none and 10 = very severe</description>
          <population>The Modified Intent-to-Treat (mITT) population included all randomized patients who received ≥ 1 dose of study drug and ≥ 1 post-baseline BM assessment was the primary analysis population analyzed for efficacy endpoints.</population>
          <units>score on a scale</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="84"/>
                <count group_id="O2" value="83"/>
                <count group_id="O3" value="86"/>
                <count group_id="O4" value="85"/>
                <count group_id="O5" value="85"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.7" spread="0.23"/>
                    <measurement group_id="O2" value="-1.5" spread="0.23"/>
                    <measurement group_id="O3" value="-2.2" spread="0.23"/>
                    <measurement group_id="O4" value="-2.1" spread="0.24"/>
                    <measurement group_id="O5" value="-1.3" spread="0.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>12 weeks</time_frame>
      <desc>A total of 428 patients were randomized and received at least one dose of medication except for one patient in the 0.3 mg plecanatide group. Therefore, a total of 427 patients were included in the safety population for adverse events reporting.</desc>
      <group_list>
        <group group_id="E1">
          <title>Plecanatide 0.3mg</title>
          <description>Plecanatide 0.3mg, one tablet by mouth daily for 12 weeks&#xD;
Plecanatide</description>
        </group>
        <group group_id="E2">
          <title>Plecanatide 1.0mg</title>
          <description>Plecanatide 1.0mg one tablet by mouth daily for 12 weeks&#xD;
Plecanatide</description>
        </group>
        <group group_id="E3">
          <title>Plecanatide 3.0mg</title>
          <description>Plecanatide 3.0mg, one tablet by mouth daily for 12 weeks&#xD;
Plecanatide</description>
        </group>
        <group group_id="E4">
          <title>Plecanatide 9.0mg</title>
          <description>Plecanatide 9.0mg, one tablet by mouth daily for 12 weeks&#xD;
Plecanatide</description>
        </group>
        <group group_id="E5">
          <title>Placebo</title>
          <description>Placebo, one tablet by mouth daily for 12 weeks&#xD;
Placebo</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (14.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="85"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="86"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Supraventricular tachycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="86"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis acute</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="86"/>
              </event>
              <event>
                <sub_title>Bile duct stone</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="86"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="86"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <default_vocab>MedDRA (14.0)</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="18" subjects_at_risk="85"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="85"/>
                <counts group_id="E3" subjects_affected="19" subjects_at_risk="86"/>
                <counts group_id="E4" subjects_affected="31" subjects_at_risk="85"/>
                <counts group_id="E5" subjects_affected="12" subjects_at_risk="86"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="85"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="85"/>
                <counts group_id="E3" events="9" subjects_affected="8" subjects_at_risk="86"/>
                <counts group_id="E4" events="12" subjects_affected="10" subjects_at_risk="85"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="86"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="85"/>
                <counts group_id="E5" events="6" subjects_affected="5" subjects_at_risk="86"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="85"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="86"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="85"/>
                <counts group_id="E3" events="5" subjects_affected="3" subjects_at_risk="86"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="86"/>
              </event>
              <event>
                <sub_title>Upper Respiratory Tract Infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="85"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="85"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="85"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="86"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="85"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="85"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="86"/>
              </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="85"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="85"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="86"/>
                <counts group_id="E4" events="8" subjects_affected="8" subjects_at_risk="85"/>
                <counts group_id="E5" events="4" subjects_affected="4" subjects_at_risk="86"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Oropharyngeal Pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="85"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="85"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="86"/>
              </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>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Patrick H. Griffin</name_or_title>
      <organization>Synergy Pharmaceuticals Inc.</organization>
      <phone>212-297-0020</phone>
    </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/NCT01722318
org study id: SP304-20212
nct id: NCT01722318
lead sponsor: 
has dmc: No
This is a randomized, 12-week, double-blind, placebo-controlled, dose-ranging study in
      patients with IBS-C.
This is a randomized, 12-week, double-blind, placebo-controlled, dose-ranging study in
      patients with IBS-C. Patients will undergo a Screening Period to determine eligibility. After
      completing a Screening Visit patients will undergo a 2-week Pre-Treatment assessment using
      the Interactive Voice Response System (IVRS) during which they will complete daily
      assessments of bowel movements (BMs), stool consistency (Bristol Stool Form Scale- BSFS),
      abdominal pain or abdominal discomfort and other symptoms associated with IBS-C. Data from
      the two-week IVRS Pre-treatment assessment are used to define the patient's baseline from
      which change will be determined. Patients who meet all entry criteria will be randomized to
      one of five treatment groups ( 0.3mg,1.0mg,3.0mg,9mg,or Placebo) on Day 1 of the Treatment
      Period. Patients will take an oral dose of study drug daily (QD) for 12 weeks and continue
      the daily IVRS diaries (BMs, abdominal pain, other symptoms). On Weeks 2, 4, 8, and 12,
      patients will return to the clinic to undergo safety and efficacy assessments. For 2 weeks
      after completing dosing, (i.e., Post-Treatment Period), patients will continue to complete
      daily IVRS diaries. Patients will then return to the clinical site for a final follow-up
      visit (End of Study Visit). The planned duration of participation in this study will be
      approximately 112 days from signing of informed consent through post-treatment or 145 days if
      30 day washout of a prohibited concomitant medication or stabilization of a medical condition
      is required before Pre-Treatment (up to 148 days, with all windows considered).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Change From Baseline in Weekly CSBMs Frequency Over the 12-Week Treatment Period (mITT Population)
time frame: 12 weeks Treatment Period
description: The primary efficacy endpoint was the change from baseline in the weekly CSBM frequency (CSBMs per week minus CSBMs per week at baseline) over a 12-week Treatment Period. A Complete Spontaneous Bowel Movement (CSBM) is a Bowel Movement (BM) that occurs in the absence of laxative use within 24 hours of the BM and the patient reports a feeling of complete evacuation.
measure: Change From Baseline in Abdominal Pain Intensity Scores Over 12-Week Treatment Period (mITT Population)
time frame: 12-Week Treatment Period
description: Abdominal Pain was assessed in the patient's daily response on a scale of 0 to 10 where 0 is did not experience the symptom at all and 10 is experienced the worst.
measure: Change From Baseline in Stool Consistency (BSFS) Over 12-Week Treatment Period (mITT Population)
time frame: 12-Week Treatment Period
description: The stool consistency of each bowel movement (BM) was assessed by patients using the 7-point Bristol Stool Form Scale [BSFS] from 1 to 7.
= separate hard lumps like nuts (difficult to pass)
= sausage shaped but lumpy
= like a sausage but with cracks on its surface
= like a sausage or snake, smooth and soft
= soft blobs with clear-cut edges (passed easily)
= fluffy pieces with ragged edges, a mushy stool
= watery, no solid pieces (entirely liquid)
measure: Change From Baseline in Straining Scores Over 12-Week Treatment Period (mITT Population)
time frame: 12-Week Treatment Period
description: The severity of straining (Straining Score) was rated by the patients using a 11-point scale (0-10) where 0 = none and 10 = very severe
arm group label: Plecanatide 0.3mg
arm group type: Active Comparator
description: Plecanatide 0.3mg, one tablet by mouth daily for 12 weeks
arm group label: Plecanatide 1.0mg
arm group type: Active Comparator
description: Plecanatide 1.0mg one tablet by mouth daily for 12 weeks
arm group label: Plecanatide 3.0mg
arm group type: Active Comparator
description: Plecanatide 3.0mg, one tablet by mouth daily for 12 weeks
arm group label: Plecanatide 9.0mg
arm group type: Active Comparator
description: Plecanatide 9.0mg, one tablet by mouth daily for 12 weeks
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo, one tablet by mouth daily for 12 weeks
intervention type: Drug
intervention name: Plecanatide
arm group label: Plecanatide 0.3mg
arm group label: Plecanatide 1.0mg
arm group label: Plecanatide 3.0mg
arm group label: Plecanatide 9.0mg
other name: Trulance
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Philip B Miner, MD
role: Principal Investigator
affiliation: Oklahoma Foundation for Digestive Research
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country: United States
responsible party type: Sponsor
mesh term: Irritable Bowel Syndrome
mesh term: Syndrome
mesh term: Constipation
mesh term: Plecanatide
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