<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/NCT01669811</url>
  </required_header>
  <id_info>
    <org_study_id>D961UC00002</org_study_id>
    <nct_id>NCT01669811</nct_id>
  </id_info>
  <brief_title>Compare D961H 20 mg Bid and 20 mg qd in Patients With Refractory Reflux Esophagitis (Inflammation of Lower Esophagus)</brief_title>
  <official_title>A Multicentre, Randomised, Double-blind, Parallel-group, Comparative Study to Compare the Efficacy and Safety of D961H 20 mg Twice Daily Oral Administration and D961H 20 mg Once Daily Oral Administration in Patients With Refractory Reflux Esophagitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AstraZeneca</source>
  <brief_summary>
    <textblock>
      This is a phase 3 multicentre, randomised, double-blind, parallel-group, comparative study to&#xD;
      evaluate the efficacy of esomeprazole (D961H) 20 mg twice daily and esomeprazole (D961H) 20&#xD;
      mg once daily in patients (in the form of esomeprazole magnesium salt) with refractory reflux&#xD;
      esophagitis after 8 weeks of standard Proton-pump inhibitor (PPI) therapy by assessment of&#xD;
      presence/absence of inflammation (esophagitis) at Week 8 according to the Los Angeles (LA)&#xD;
      classification&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A multicentre, randomised, double-blind, parallel-group, comparative study to compare the&#xD;
      efficacy and safety of D961H 20 mg twice daily oral administration and D961H 20 mg once daily&#xD;
      oral administration in patients with refractory reflux esophagitis&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">May 2014</completion_date>
  <primary_completion_date type="Actual">May 2014</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants With Healing of RE Who Were Graded &quot;O&quot; at Week 8 Out of Participants Who Were Graded &quot;A&quot; to &quot;D&quot; at Baseline According to Los Angeles Classification</measure>
    <time_frame>8 Weeks</time_frame>
    <description>Percentage of participants with healing of reflux esophagitis (RE) who were graded &quot;O&quot; (No RE) at Week 8 out of participants who were graded &quot;A&quot; (least severe) to &quot;D&quot; (most severe) at baseline according to Los Angeles classification</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Healing of RE Who Were Graded &quot;O&quot; at Week 4 Out of Participants Who Were Graded &quot;A&quot; to &quot;D&quot; at Baseline According to Los Angeles Classification</measure>
    <time_frame>4 Weeks</time_frame>
    <description>Percentage of participants with healing of reflux esophagitis (RE) who were graded &quot;O&quot; (No RE) at Week 4 out of participants who were graded &quot;A&quot; (least severe) to &quot;D&quot; (most severe) at baseline according to Los Angeles classification</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Heartburn at Week 4</measure>
    <time_frame>4 Weeks</time_frame>
    <description>Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -heartburn at Week 4 (on Day 29) based on the Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Acid Regurgitation at Week 4</measure>
    <time_frame>4 Weeks</time_frame>
    <description>Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -acid regurgitation at Week 4 (on Day 29) based on the Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Abdominal Pain at Week 4</measure>
    <time_frame>4 Weeks</time_frame>
    <description>Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -abdominal pain at Week 4 (on Day 29) based on the Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Difficulty of Swallowing at Week 4</measure>
    <time_frame>4 Weeks</time_frame>
    <description>Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -difficulty of swallowing at Week 4 (on Day 29) based on the Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Sleep Disturbance at Week 4</measure>
    <time_frame>4 Weeks</time_frame>
    <description>Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -sleep disturbance at Week 4 (on Day 29) based on the Kaplan-Meier method.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1398</enrollment>
  <condition>Refractory Reflux Esophagitis</condition>
  <arm_group>
    <arm_group_label>D961H 20mg twice daily</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Double-blinded</description>
  </arm_group>
  <arm_group>
    <arm_group_label>D961H 20mg once daily</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Double-blinded</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Esomeprazole (D961H) twice daily</intervention_name>
    <description>One capsule of esomeprazole 20 mg (in the form of esomeprazole magnesium salt) will be administered in the morning and in the evening</description>
    <arm_group_label>D961H 20mg twice daily</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Esomeprazole (D961H) once daily</intervention_name>
    <description>One capsule of esomeprazole 20 mg (in the form of esomeprazole magnesium salt) will be administered in the morning and one corresponding placebo capsule in the evening</description>
    <arm_group_label>D961H 20mg once daily</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provision of informed consent prior to any study specific procedures.&#xD;
&#xD;
          2. Patients with RE classified into LA classification Grade A, B, C or D by Endoscopy&#xD;
             despite of at least 8-week treatment using standard doses of PPIs.&#xD;
&#xD;
          3. Patients must fulfill at least one of the following criteria such as (i) RE with LA&#xD;
             grade C/D at Endoscopy on visit 1 and/or history of RE with LA grade C/D, (ii) RE was&#xD;
             diagnosed more than 1 year before visit 1.&#xD;
&#xD;
          4. Patients who are able to complete the Patient Diary&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Male or female aged less than 20 years at the time of informed consent.&#xD;
&#xD;
          2. Patients with current evidence of the gastrointestinal diseases/conditions such as&#xD;
             esophageal stricture to interfere with the evaluation of the study etc&#xD;
&#xD;
          3. Gastric or duodenal ulcer verified by Endoscopy within 12 weeks before randomisation.&#xD;
&#xD;
          4. Previous esophageal, gastric or duodenal surgery except simple closure of perforated&#xD;
             ulcer, simple endoscopic treatment with simple operation etc&#xD;
&#xD;
          5. Current or historical evidence (within 12 weeks prior to randomisation) of the&#xD;
             diseases/conditions as judged to interfere with the evaluation of the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tore Lind, MSD</last_name>
    <role>Study Director</role>
    <affiliation>AstraZeneca, Moelndal, Sweden</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Lan Chen</last_name>
    <role>Study Director</role>
    <affiliation>AstraZeneca, Osaka, Japan</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Yoshikazu Kinoshita, PROFESSOR OF MEDICINE</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dept of Gastroenterology and Hepatology, Shimane, Japan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Abiko-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Adachi-ku</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Annaka-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Asahikawa-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Asakura-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Beppu-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bunkyo-ku</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Chuo-ku</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Fujiidera-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Fukuoka-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Fukushima-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Gifu-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hamamatsu-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hirakata-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hitachi-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ibara-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ichiki-Kushikino-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ishikari-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Iwata-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Izumo-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kagoshima-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kamakura-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kanazawa-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Karatsu-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kawasaki-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kirishima-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kita-ku</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kobe-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kochi-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Koga-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Koriyama-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kumagaya-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kumamoto-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kyoto-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Machida-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Matsumoto-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Meguro-ku</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Moriguchi-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nishinomiya-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ogori-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Oita-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Okayama-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Osaka-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ota-ku</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Otawara-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Saga-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Saitama-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sakaide-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Saku-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sapporo-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sendai-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Shibuya-ku</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Shinagawa-ku</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Shinjuku-ku</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Takasaki-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Takatsuki-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Toshima-ku</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Toyama-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Uji-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Wakayama-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Yanagawa-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Yokohama-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Yufu-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <link>
    <url>http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&amp;studyid=712&amp;filename=D961UC00002_Synopsis.pdf</url>
    <description>D961UC00002_Synopsis</description>
  </link>
  <verification_date>August 2015</verification_date>
  <study_first_submitted>August 17, 2012</study_first_submitted>
  <study_first_submitted_qc>August 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 21, 2012</study_first_posted>
  <results_first_submitted>May 18, 2015</results_first_submitted>
  <results_first_submitted_qc>July 20, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">August 14, 2015</results_first_posted>
  <last_update_submitted>August 19, 2015</last_update_submitted>
  <last_update_submitted_qc>August 19, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 27, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Refractory Reflux Esophagitis,</keyword>
  <keyword>Japanese,</keyword>
  <keyword>Nexium,</keyword>
  <keyword>twice daily,</keyword>
  <keyword>oral administration</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gastroesophageal Reflux</mesh_term>
    <mesh_term>Esophagitis</mesh_term>
    <mesh_term>Esophagitis, Peptic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Esomeprazole</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>First subject enrolled on 25 August 2012. Last subject completed on 30 May 2014.</recruitment_details>
      <pre_assignment_details>Out of 1398 enrolled subjects, 287 subjects were randomised and 1111 subjects were not randomised. The reasons of no randomisation were 'Eligibilty criteria not met' (1067 subjects), 'Subject decision' (37 subjects), 'Adverse event' (2 subjects) and other reasons (5 subjects).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>D961H 20 mg BID</title>
          <description>Hard capsule containing 22.3 mg of D961H as enteric coated pellets</description>
        </group>
        <group group_id="P2">
          <title>D961H 20 mg QD + Placebo</title>
          <description>Hard capsule unidentifiable to D961H capsule 20 mg</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="145"/>
                <participants group_id="P2" count="142"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="142"/>
                <participants group_id="P2" count="131"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Investigator decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Eligibility Criteria Not Fulfilled</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>It was found that 2 patients in D961H 20 mg QD + Placebo group had no refractory RE after randomisation. Therefore, these two patients were excluded from the full analysis set, which was the primary analysis set of this study and was used for summaries of baseline characteristics and outcome measures.</population>
      <group_list>
        <group group_id="B1">
          <title>D961H 20 mg BID</title>
          <description>D961H 20 mg twice Daily</description>
        </group>
        <group group_id="B2">
          <title>D961H 20 mg QD + Placebo</title>
          <description>D961H 20 mg once daily along with placebo</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="145"/>
            <count group_id="B2" value="140"/>
            <count group_id="B3" value="285"/>
          </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="64.7" spread="13.87" lower_limit="32" upper_limit="90"/>
                    <measurement group_id="B2" value="61.7" spread="14.72" lower_limit="24" upper_limit="91"/>
                    <measurement group_id="B3" value="63.2" spread="14.35" lower_limit="24" upper_limit="91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>&lt;65</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="68"/>
                    <measurement group_id="B2" value="69"/>
                    <measurement group_id="B3" value="137"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=65</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="77"/>
                    <measurement group_id="B2" value="71"/>
                    <measurement group_id="B3" value="148"/>
                  </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="69"/>
                    <measurement group_id="B2" value="70"/>
                    <measurement group_id="B3" value="139"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="76"/>
                    <measurement group_id="B2" value="70"/>
                    <measurement group_id="B3" value="146"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="145"/>
                    <measurement group_id="B2" value="140"/>
                    <measurement group_id="B3" value="285"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Healing of RE Who Were Graded &quot;O&quot; at Week 8 Out of Participants Who Were Graded &quot;A&quot; to &quot;D&quot; at Baseline According to Los Angeles Classification</title>
        <description>Percentage of participants with healing of reflux esophagitis (RE) who were graded &quot;O&quot; (No RE) at Week 8 out of participants who were graded &quot;A&quot; (least severe) to &quot;D&quot; (most severe) at baseline according to Los Angeles classification</description>
        <time_frame>8 Weeks</time_frame>
        <population>Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who had at least one dose of investigational product</population>
        <group_list>
          <group group_id="O1">
            <title>D961H 20mg Bid</title>
            <description>D961H 20mg twice daily</description>
          </group>
          <group group_id="O2">
            <title>D961H 20mg QD + Placebo</title>
            <description>D961H 20mg once daily along with placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Healing of RE Who Were Graded &quot;O&quot; at Week 8 Out of Participants Who Were Graded &quot;A&quot; to &quot;D&quot; at Baseline According to Los Angeles Classification</title>
          <description>Percentage of participants with healing of reflux esophagitis (RE) who were graded &quot;O&quot; (No RE) at Week 8 out of participants who were graded &quot;A&quot; (least severe) to &quot;D&quot; (most severe) at baseline according to Los Angeles classification</description>
          <population>Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who had at least one dose of investigational product</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="145"/>
                <count group_id="O2" value="140"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92.4" lower_limit="86.9" upper_limit="95.7"/>
                    <measurement group_id="O2" value="68.6" lower_limit="60.5" upper_limit="75.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>To evaluate the efficacy of D20 bid on healing of refractory RE in comparison with D20 qd</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>p-value is obtained using chi square method.</p_value_desc>
            <method>Chi-squared</method>
            <method_desc>95% CI is obtained using Newcombe-Wilson score method without continuity correction.</method_desc>
            <param_type>Difference in proportions</param_type>
            <param_value>23.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>14.9</ci_lower_limit>
            <ci_upper_limit>32.6</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Healing of RE Who Were Graded &quot;O&quot; at Week 4 Out of Participants Who Were Graded &quot;A&quot; to &quot;D&quot; at Baseline According to Los Angeles Classification</title>
        <description>Percentage of participants with healing of reflux esophagitis (RE) who were graded &quot;O&quot; (No RE) at Week 4 out of participants who were graded &quot;A&quot; (least severe) to &quot;D&quot; (most severe) at baseline according to Los Angeles classification</description>
        <time_frame>4 Weeks</time_frame>
        <population>Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who had at least one dose of investigational product</population>
        <group_list>
          <group group_id="O1">
            <title>D961H 20mg Bid</title>
            <description>D961H 20mg twice daily</description>
          </group>
          <group group_id="O2">
            <title>D961H 20mg QD + Placebo</title>
            <description>D961H 20mg once daily along with placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Healing of RE Who Were Graded &quot;O&quot; at Week 4 Out of Participants Who Were Graded &quot;A&quot; to &quot;D&quot; at Baseline According to Los Angeles Classification</title>
          <description>Percentage of participants with healing of reflux esophagitis (RE) who were graded &quot;O&quot; (No RE) at Week 4 out of participants who were graded &quot;A&quot; (least severe) to &quot;D&quot; (most severe) at baseline according to Los Angeles classification</description>
          <population>Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who had at least one dose of investigational product</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="145"/>
                <count group_id="O2" value="140"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="81.4" lower_limit="74.3" upper_limit="86.9"/>
                    <measurement group_id="O2" value="48.6" lower_limit="40.4" upper_limit="56.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>To evaluate the efficacy of D20 bid on healing of refractory RE in comparison with D20 qd</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>p-value is obtained using chi square method.</p_value_desc>
            <method>Chi-squared</method>
            <method_desc>95% CI is obtained using Newcombe-Wilson score method without continuity correction.</method_desc>
            <param_type>Difference in proportions</param_type>
            <param_value>32.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>21.9</ci_lower_limit>
            <ci_upper_limit>42.6</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Heartburn at Week 4</title>
        <description>Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -heartburn at Week 4 (on Day 29) based on the Kaplan-Meier method.</description>
        <time_frame>4 Weeks</time_frame>
        <population>Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who took at least one dose of investigational product. However, out of these participants, only participants who had the GERD symptom -heartburn at baseline were included.</population>
        <group_list>
          <group group_id="O1">
            <title>D961H 20mg Bid</title>
            <description>D961H 20mg twice daily</description>
          </group>
          <group group_id="O2">
            <title>D961H 20mg QD + Placebo</title>
            <description>D961H 20mg once daily along with placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Heartburn at Week 4</title>
          <description>Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -heartburn at Week 4 (on Day 29) based on the Kaplan-Meier method.</description>
          <population>Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who took at least one dose of investigational product. However, out of these participants, only participants who had the GERD symptom -heartburn at baseline were included.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="90"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="81.1" lower_limit="74.3" upper_limit="86.9"/>
                    <measurement group_id="O2" value="72.8" lower_limit="40.4" upper_limit="56.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>To evaluate the efficacy of D20 bid on gastroesophageal reflux disease (GERD) symptoms in comparison with D20 qd</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.1452</p_value>
            <method>Log Rank</method>
            <method_desc>95% CI of the hazard ratio is obtained using Cox proportional hazards model including a factor of treatment group.</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.29</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.91</ci_lower_limit>
            <ci_upper_limit>1.83</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Acid Regurgitation at Week 4</title>
        <description>Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -acid regurgitation at Week 4 (on Day 29) based on the Kaplan-Meier method.</description>
        <time_frame>4 Weeks</time_frame>
        <population>Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who took at least one dose of investigational product. However, out of these participants, only participants who had the GERD symptom -acid regurgitation at baseline were included.</population>
        <group_list>
          <group group_id="O1">
            <title>D961H 20mg Bid</title>
            <description>D961H 20mg twice daily</description>
          </group>
          <group group_id="O2">
            <title>D961H 20mg QD + Placebo</title>
            <description>D961H 20mg once daily along with placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Acid Regurgitation at Week 4</title>
          <description>Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -acid regurgitation at Week 4 (on Day 29) based on the Kaplan-Meier method.</description>
          <population>Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who took at least one dose of investigational product. However, out of these participants, only participants who had the GERD symptom -acid regurgitation at baseline were included.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="78"/>
                <count group_id="O2" value="67"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="73.1" lower_limit="74.3" upper_limit="86.9"/>
                    <measurement group_id="O2" value="61.2" lower_limit="40.4" upper_limit="56.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>To evaluate the efficacy of D20 bid on gastroesophageal reflux disease (GERD) symptoms in comparison with D20 qd</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0837</p_value>
            <method>Log Rank</method>
            <method_desc>95% CI of the hazard ratio is obtained using Cox proportional hazards model including a factor of treatment group.</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.46</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.97</ci_lower_limit>
            <ci_upper_limit>2.18</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Abdominal Pain at Week 4</title>
        <description>Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -abdominal pain at Week 4 (on Day 29) based on the Kaplan-Meier method.</description>
        <time_frame>4 Weeks</time_frame>
        <population>Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who took at least one dose of investigational product. However, out of these participants, only participants who had the GERD symptom -abdominal pain at baseline were included.</population>
        <group_list>
          <group group_id="O1">
            <title>D961H 20mg Bid</title>
            <description>D961H 20mg twice daily</description>
          </group>
          <group group_id="O2">
            <title>D961H 20mg QD + Placebo</title>
            <description>D961H 20mg once daily along with placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Abdominal Pain at Week 4</title>
          <description>Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -abdominal pain at Week 4 (on Day 29) based on the Kaplan-Meier method.</description>
          <population>Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who took at least one dose of investigational product. However, out of these participants, only participants who had the GERD symptom -abdominal pain at baseline were included.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="47"/>
                <count group_id="O2" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68.1" lower_limit="74.3" upper_limit="86.9"/>
                    <measurement group_id="O2" value="59.1" lower_limit="40.4" upper_limit="56.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>To evaluate the efficacy of D20 bid on gastroesophageal reflux disease (GERD) symptoms in comparison with D20 qd</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.2678</p_value>
            <method>Log Rank</method>
            <method_desc>95% CI of the hazard ratio is obtained using Cox proportional hazards model including a factor of treatment group.</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.34</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.80</ci_lower_limit>
            <ci_upper_limit>2.26</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Difficulty of Swallowing at Week 4</title>
        <description>Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -difficulty of swallowing at Week 4 (on Day 29) based on the Kaplan-Meier method.</description>
        <time_frame>4 Weeks</time_frame>
        <population>Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who took at least one dose of investigational product. However, out of these participants, only participants who had the GERD symptom -difficulty of swallowing at baseline were included.</population>
        <group_list>
          <group group_id="O1">
            <title>D961H 20mg Bid</title>
            <description>D961H 20mg twice daily</description>
          </group>
          <group group_id="O2">
            <title>D961H 20mg QD + Placebo</title>
            <description>D961H 20mg once daily along with placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Difficulty of Swallowing at Week 4</title>
          <description>Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -difficulty of swallowing at Week 4 (on Day 29) based on the Kaplan-Meier method.</description>
          <population>Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who took at least one dose of investigational product. However, out of these participants, only participants who had the GERD symptom -difficulty of swallowing at baseline were included.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="78.6" lower_limit="74.3" upper_limit="86.9"/>
                    <measurement group_id="O2" value="74.1" lower_limit="40.4" upper_limit="56.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>To evaluate the efficacy of D20 bid on gastroesophageal reflux disease (GERD) symptoms in comparison with D20 qd</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.6389</p_value>
            <method>Log Rank</method>
            <method_desc>95% CI of the hazard ratio is obtained using Cox proportional hazards model including a factor of treatment group.</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.15</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.62</ci_lower_limit>
            <ci_upper_limit>2.12</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Sleep Disturbance at Week 4</title>
        <description>Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -sleep disturbance at Week 4 (on Day 29) based on the Kaplan-Meier method.</description>
        <time_frame>4 Weeks</time_frame>
        <population>Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who took at least one dose of investigational product. However, out of these participants, only participants who had the GERD symptom -sleep disturbance at baseline were included.</population>
        <group_list>
          <group group_id="O1">
            <title>D961H 20mg Bid</title>
            <description>D961H 20mg twice daily</description>
          </group>
          <group group_id="O2">
            <title>D961H 20mg QD + Placebo</title>
            <description>D961H 20mg once daily along with placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Sleep Disturbance at Week 4</title>
          <description>Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -sleep disturbance at Week 4 (on Day 29) based on the Kaplan-Meier method.</description>
          <population>Included all of the randomised participants who were definitely diagnosed to have refractory RE before the randomisation and who took at least one dose of investigational product. However, out of these participants, only participants who had the GERD symptom -sleep disturbance at baseline were included.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="91.2" lower_limit="74.3" upper_limit="86.9"/>
                    <measurement group_id="O2" value="89.3" lower_limit="40.4" upper_limit="56.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>To evaluate the efficacy of D20 bid on gastroesophageal reflux disease (GERD) symptoms in comparison with D20 qd</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.4485</p_value>
            <method>Log Rank</method>
            <method_desc>95% CI of the hazard ratio is obtained using Cox proportional hazards model including a factor of treatment group.</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.38</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.80</ci_lower_limit>
            <ci_upper_limit>2.38</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>D961H 20 mg BID</title>
          <description>D961H 20 mg twice Daily</description>
        </group>
        <group group_id="E2">
          <title>D961H 20 mg QD + Placebo</title>
          <description>D961H 20 mg once daily along with placebo</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 17.0</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="145"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="142"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="145"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="142"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="145"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="142"/>
              </event>
              <event>
                <sub_title>Pancreatic pseudocyst</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="145"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="142"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Parotid abscess</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="145"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="142"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 17.0</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="8" subjects_at_risk="145"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="142"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="145"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="142"/>
              </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>All PIs were prohibited to disclose all information related to this study withiout AZ approval before this study was completed.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Masahiro Nii</name_or_title>
      <organization>Clinical Statistics &amp; Programming Department, Clinical Science Division, R&amp;D, AstraZeneca Japan</organization>
      <email>Masahiro.Nii@astrazeneca.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/NCT01669811
org study id: D961UC00002
nct id: NCT01669811
lead sponsor: 
This is a phase 3 multicentre, randomised, double-blind, parallel-group, comparative study to
      evaluate the efficacy of esomeprazole (D961H) 20 mg twice daily and esomeprazole (D961H) 20
      mg once daily in patients (in the form of esomeprazole magnesium salt) with refractory reflux
      esophagitis after 8 weeks of standard Proton-pump inhibitor (PPI) therapy by assessment of
      presence/absence of inflammation (esophagitis) at Week 8 according to the Los Angeles (LA)
      classification
A multicentre, randomised, double-blind, parallel-group, comparative study to compare the
      efficacy and safety of D961H 20 mg twice daily oral administration and D961H 20 mg once daily
      oral administration in patients with refractory reflux esophagitis
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Percentage of Participants With Healing of RE Who Were Graded "O" at Week 8 Out of Participants Who Were Graded "A" to "D" at Baseline According to Los Angeles Classification
time frame: 8 Weeks
description: Percentage of participants with healing of reflux esophagitis (RE) who were graded "O" (No RE) at Week 8 out of participants who were graded "A" (least severe) to "D" (most severe) at baseline according to Los Angeles classification
measure: Percentage of Participants With Healing of RE Who Were Graded "O" at Week 4 Out of Participants Who Were Graded "A" to "D" at Baseline According to Los Angeles Classification
time frame: 4 Weeks
description: Percentage of participants with healing of reflux esophagitis (RE) who were graded "O" (No RE) at Week 4 out of participants who were graded "A" (least severe) to "D" (most severe) at baseline according to Los Angeles classification
measure: Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Heartburn at Week 4
time frame: 4 Weeks
description: Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -heartburn at Week 4 (on Day 29) based on the Kaplan-Meier method.
measure: Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Acid Regurgitation at Week 4
time frame: 4 Weeks
description: Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -acid regurgitation at Week 4 (on Day 29) based on the Kaplan-Meier method.
measure: Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Abdominal Pain at Week 4
time frame: 4 Weeks
description: Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -abdominal pain at Week 4 (on Day 29) based on the Kaplan-Meier method.
measure: Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Difficulty of Swallowing at Week 4
time frame: 4 Weeks
description: Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -difficulty of swallowing at Week 4 (on Day 29) based on the Kaplan-Meier method.
measure: Cumulative Percentage of Participants Who Had Sustained Resolution of GERD Symptom -Sleep Disturbance at Week 4
time frame: 4 Weeks
description: Cumulative percentage of participants who had sustained resolution (defined as at least 7-day consecutive symptom free) of gastroesophageal reflux disease (GERD) symptom -sleep disturbance at Week 4 (on Day 29) based on the Kaplan-Meier method.
arm group label: D961H 20mg twice daily
arm group type: Experimental
description: Double-blinded
arm group label: D961H 20mg once daily
arm group type: Active Comparator
description: Double-blinded
intervention type: Drug
intervention name: Esomeprazole (D961H) twice daily
description: One capsule of esomeprazole 20 mg (in the form of esomeprazole magnesium salt) will be administered in the morning and in the evening
arm group label: D961H 20mg twice daily
intervention type: Drug
intervention name: Esomeprazole (D961H) once daily
description: One capsule of esomeprazole 20 mg (in the form of esomeprazole magnesium salt) will be administered in the morning and one corresponding placebo capsule in the evening
arm group label: D961H 20mg once daily
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Tore Lind, MSD
role: Study Director
affiliation: AstraZeneca, Moelndal, Sweden
last name: Lan Chen
role: Study Director
affiliation: AstraZeneca, Osaka, Japan
last name: Yoshikazu Kinoshita, PROFESSOR OF MEDICINE
role: Principal Investigator
affiliation: Dept of Gastroenterology and Hepatology, Shimane, Japan
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country: Japan
url: http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=712&filename=D961UC00002_Synopsis.pdf
description: D961UC00002_Synopsis
responsible party type: Sponsor
mesh term: Gastroesophageal Reflux
mesh term: Esophagitis
mesh term: Esophagitis, Peptic
mesh term: Esomeprazole
participant flow: 
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reported events: 
certain agreements: 
point of contact: 