<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/NCT02262169</url>
  </required_header>
  <id_info>
    <org_study_id>DLBS2411-0313</org_study_id>
    <nct_id>NCT02262169</nct_id>
  </id_info>
  <brief_title>DLBS2411 Treatment for Ulcer Healing in Non-Bleeding Peptic Ulcers</brief_title>
  <official_title>DLBS2411 Treatment for Ulcer Healing in Non-Bleeding Peptic Ulcers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dexa Medica Group</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Dexa Medica Group</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a 2-arm, prospective, double-blind, double-dummy, randomized-controlled study using&#xD;
      DLBS2411 at a dose of 250 mg twice daily (before morning and evening meals), or omeprazole at&#xD;
      a dose of 40 mg once daily (before morning meal), for an 8-week course of therapy, for the&#xD;
      treatment of patients with any non-bleeding peptic ulcers.&#xD;
&#xD;
      DLBS2411 is a bioactive fraction of an Indonesian native herbal, Cinnamomum burmanii, locally&#xD;
      known as kayu manis have been proven at cellular and genetic levels to have an antiulcer&#xD;
      effect through both suppressing the gastric acidity and enhancing gastric mucosal protection.&#xD;
      The anti-secretory effect of DLBS2411 is exerted through the inhibition of H+/K+ ATPase&#xD;
      'pump' as well as down-regulation of the H+/K+ ATPase gene expression, thus suppressing&#xD;
      gastric acid secretion; while its gastro-protective defense mechanism works through the&#xD;
      promotion of COX-2 derived prostaglandin (PgE2) synthesis, stimulating gastric-epithelial&#xD;
      mucous and bicarbonate secretion; anti-oxidative activity; and endothelial-nitric oxide (NO)&#xD;
      formation.&#xD;
&#xD;
      Recent study of DLBS2411 in healthy volunteers demonstrated the effective role and safety of&#xD;
      DLBS2411 in suppressing intragastric acidity. Having such mechanisms of action, DLBS2411 is&#xD;
      hypothesized to benefit in peptic ulcers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A total of 140 subjects will be allocated into 2 groups of treatment; each group will consist&#xD;
      of 70 subjects with the treatment regimens:&#xD;
&#xD;
      Treatment I : 2 capsules of Omeprazole 20 mg, once daily and 1 placebo caplet of DLBS2411,&#xD;
      twice daily Treatment II : 1 caplet of DLBS2411 250 mg, twice daily and 2 placebo capsules of&#xD;
      omeprazole, once daily&#xD;
&#xD;
      DLBS2411 will be administered twice daily at least 30 minutes before morning and evening&#xD;
      meals, while omeprazole, once daily before morning meals, for 8 weeks of study period.&#xD;
&#xD;
      The eligible subjects will receive either study medication (Treatment 1 or Treatment 2), for&#xD;
      8 weeks of treatment; and will be instructed to come to the clinic every 4-week interval&#xD;
      throughout the study period.&#xD;
&#xD;
      Subjects will be evaluated for treatment efficacy at baseline and at interval of 4 weeks over&#xD;
      the 8-week course of therapy.&#xD;
&#xD;
      The safety profile of study medication other than vital signs and adverse event will be&#xD;
      measured at baseline and end of study. Vital signs and adverse event will be measured at&#xD;
      baseline and every follow-up visit including end of study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    This study was terminated due to internal technical issues at study site&#xD;
  </why_stopped>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">March 2019</completion_date>
  <primary_completion_date type="Actual">February 2019</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>Endoscopic ulcer healing rate</measure>
    <time_frame>8 weeks</time_frame>
    <description>Endoscopic ulcer healing rate after 8 weeks of treatment. Ulcer healing rate is defined as the proportion of subjects with complete ulcer-healing (referring to S1 or S2 Scarring stage according to Sakita-Fukutomi classification) as confirmed by endoscopic finding.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The improvement rate of each of gastric symptoms</measure>
    <time_frame>4 and 8 weeks</time_frame>
    <description>The improvement rate of each of gastric symptoms at each of the follow-up visits (after 4 and 8 weeks of treatment):&#xD;
abdominal or epigastric pain (middle or upper stomach)&#xD;
nausea or vomiting,&#xD;
bloating</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The quality of ulcer healing</measure>
    <time_frame>8 weeks</time_frame>
    <description>The quality of ulcer healing as measured by the levels of gastric mucosal bFGF (basic fibroblast growth factor) and COX-2 (cyclo-oxygenase), at baseline and Week 8 of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mucosal thickness</measure>
    <time_frame>8 weeks</time_frame>
    <description>Gastric mucosal thickness will be measured quantitatively as the expression of MUC5AC by immunohistochemistry (IHC) method, at baseline and Week 8 of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients' global evaluation for their symptoms</measure>
    <time_frame>4 and 8 weeks</time_frame>
    <description>Patients' global evaluation for their symptoms categorized as: no improvement or slightly improved or moderately improved or markedly improved, at Week 4 and 8 (end of study).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Liver function</measure>
    <time_frame>8 weeks</time_frame>
    <description>Liver function (serum ALT (alanine-aminotransferase), serum AST (aspartate-aminotransferase), alkaline phosphatase, total bilirubin) at baseline and at the end of study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal function</measure>
    <time_frame>8 weeks</time_frame>
    <description>Renal function (serum creatinine and BUN (blood urea nitrogen) level) at baseline and at the end of study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>4 and 8 weeks</time_frame>
    <description>Adverse event, will be observed throughout the study conduct</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Non-Bleeding Peptic Ulcers</condition>
  <arm_group>
    <arm_group_label>Treatment I</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>2 Omeprazole capsules 20 mg once daily and 1 placebo caplet of DLBS2411, twice daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment II</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 DLBS2411 caplet 250 mg twice daily and 2 placebo capsules of Omeprazole once daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Omeprazole</intervention_name>
    <description>2 Omeprazole capsules 20 mg, once daily</description>
    <arm_group_label>Treatment I</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo caplet of DLBS2411</intervention_name>
    <description>1 placebo caplet of DLBS2411, twice daily</description>
    <arm_group_label>Treatment I</arm_group_label>
    <other_name>Placebo caplet of Redacid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DLBS2411</intervention_name>
    <description>1 DLBS2411 caplet 250 mg, twice daily</description>
    <arm_group_label>Treatment II</arm_group_label>
    <other_name>Redacid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo capsule of Omeprazole</intervention_name>
    <description>2 placebo capsules of Omeprazole, once daily</description>
    <arm_group_label>Treatment II</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female subjects aged 18-75 years old.&#xD;
&#xD;
          -  Diagnosed as non-bleeding peptic ulcers who do not require endoscopic therapy, as&#xD;
             confirmed by :&#xD;
&#xD;
               -  The presence of endoscopically confirmed gastric or duodenal ulcer(s) at size(s)&#xD;
                  of at least 3 mm or larger.&#xD;
&#xD;
          -  Subjects with low-risk of recurrent bleeding, defined as both:&#xD;
&#xD;
               -  Complete Rockall score of ≤ 7.&#xD;
&#xD;
               -  Endoscopic stigmata (lesion) of grade II-C or III based on Forrest&#xD;
                  classification.&#xD;
&#xD;
          -  Able to take oral medication.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  For females of childbearing potential: pregnancy, breast-feeding, the intention of&#xD;
             becoming pregnant during the study participation.&#xD;
&#xD;
               -  Patients must accept pregnancy tests during the trial if menstrual cycle is&#xD;
                  missed&#xD;
&#xD;
               -  Fertile patients must use a reliable and effective contraceptive&#xD;
&#xD;
          -  History of or known or suspected Zollinger Ellison syndrome.&#xD;
&#xD;
          -  History of endoscopic therapy for bleeding ulcer within the past 4 weeks.&#xD;
&#xD;
          -  Indication for endoscopic hemostasis therapy.&#xD;
&#xD;
          -  Presence of Helicobacter pylori infection&#xD;
&#xD;
          -  History of or known coronary artery disease (CAD), congestive heart failure, pulmonary&#xD;
             disease, and any other uncontrolled chronic diseases.&#xD;
&#xD;
          -  History of or known gastrointestinal malignancy or ulcers associated to malignancy.&#xD;
&#xD;
          -  Currently known being afflicted by serious infection(s).&#xD;
&#xD;
          -  Inadequate liver function&#xD;
&#xD;
          -  Inadequate renal function&#xD;
&#xD;
          -  Subjects being under therapy with any herbal medicines.&#xD;
&#xD;
          -  Known hypersensitivity or idiosyncratic reaction or adverse drug reactions to proton&#xD;
             pump inhibitors (PPIs).&#xD;
&#xD;
          -  Participation in any other clinical studies within 30 days prior to 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>IDN Wibawa Prof. DR. Dr., SpPD-KGEH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Division of Gastroenterohepatology Department of Internal Medicine Faculty of Medicine, University of Udayana Sanglah General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Division of Gastroenterohepatology Department of Internal Medicine Faculty of Medicine, University of Udayana Sanglah General Hospital</name>
      <address>
        <city>Denpasar</city>
        <state>Bali</state>
        <zip>80114</zip>
        <country>Indonesia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Indonesia</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>October 7, 2014</study_first_submitted>
  <study_first_submitted_qc>October 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2014</study_first_posted>
  <last_update_submitted>July 5, 2019</last_update_submitted>
  <last_update_submitted_qc>July 5, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 9, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Non-Bleeding Peptic Ulcers, DLBS2411, Ulcer Healing</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Peptic Ulcer</mesh_term>
    <mesh_term>Ulcer</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Omeprazole</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02262169
org study id: DLBS2411-0313
nct id: NCT02262169
lead sponsor: 
has dmc: No
This is a 2-arm, prospective, double-blind, double-dummy, randomized-controlled study using
      DLBS2411 at a dose of 250 mg twice daily (before morning and evening meals), or omeprazole at
      a dose of 40 mg once daily (before morning meal), for an 8-week course of therapy, for the
      treatment of patients with any non-bleeding peptic ulcers.

      DLBS2411 is a bioactive fraction of an Indonesian native herbal, Cinnamomum burmanii, locally
      known as kayu manis have been proven at cellular and genetic levels to have an antiulcer
      effect through both suppressing the gastric acidity and enhancing gastric mucosal protection.
      The anti-secretory effect of DLBS2411 is exerted through the inhibition of H+/K+ ATPase
      'pump' as well as down-regulation of the H+/K+ ATPase gene expression, thus suppressing
      gastric acid secretion; while its gastro-protective defense mechanism works through the
      promotion of COX-2 derived prostaglandin (PgE2) synthesis, stimulating gastric-epithelial
      mucous and bicarbonate secretion; anti-oxidative activity; and endothelial-nitric oxide (NO)
      formation.

      Recent study of DLBS2411 in healthy volunteers demonstrated the effective role and safety of
      DLBS2411 in suppressing intragastric acidity. Having such mechanisms of action, DLBS2411 is
      hypothesized to benefit in peptic ulcers.
A total of 140 subjects will be allocated into 2 groups of treatment; each group will consist
      of 70 subjects with the treatment regimens:

      Treatment I : 2 capsules of Omeprazole 20 mg, once daily and 1 placebo caplet of DLBS2411,
      twice daily Treatment II : 1 caplet of DLBS2411 250 mg, twice daily and 2 placebo capsules of
      omeprazole, once daily

      DLBS2411 will be administered twice daily at least 30 minutes before morning and evening
      meals, while omeprazole, once daily before morning meals, for 8 weeks of study period.

      The eligible subjects will receive either study medication (Treatment 1 or Treatment 2), for
      8 weeks of treatment; and will be instructed to come to the clinic every 4-week interval
      throughout the study period.

      Subjects will be evaluated for treatment efficacy at baseline and at interval of 4 weeks over
      the 8-week course of therapy.

      The safety profile of study medication other than vital signs and adverse event will be
      measured at baseline and end of study. Vital signs and adverse event will be measured at
      baseline and every follow-up visit including end of study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Endoscopic ulcer healing rate
time frame: 8 weeks
description: Endoscopic ulcer healing rate after 8 weeks of treatment. Ulcer healing rate is defined as the proportion of subjects with complete ulcer-healing (referring to S1 or S2 Scarring stage according to Sakita-Fukutomi classification) as confirmed by endoscopic finding.
measure: The improvement rate of each of gastric symptoms
time frame: 4 and 8 weeks
description: The improvement rate of each of gastric symptoms at each of the follow-up visits (after 4 and 8 weeks of treatment):
abdominal or epigastric pain (middle or upper stomach)
nausea or vomiting,
bloating
measure: The quality of ulcer healing
time frame: 8 weeks
description: The quality of ulcer healing as measured by the levels of gastric mucosal bFGF (basic fibroblast growth factor) and COX-2 (cyclo-oxygenase), at baseline and Week 8 of treatment.
measure: Mucosal thickness
time frame: 8 weeks
description: Gastric mucosal thickness will be measured quantitatively as the expression of MUC5AC by immunohistochemistry (IHC) method, at baseline and Week 8 of treatment.
measure: Patients' global evaluation for their symptoms
time frame: 4 and 8 weeks
description: Patients' global evaluation for their symptoms categorized as: no improvement or slightly improved or moderately improved or markedly improved, at Week 4 and 8 (end of study).
measure: Liver function
time frame: 8 weeks
description: Liver function (serum ALT (alanine-aminotransferase), serum AST (aspartate-aminotransferase), alkaline phosphatase, total bilirubin) at baseline and at the end of study
measure: Renal function
time frame: 8 weeks
description: Renal function (serum creatinine and BUN (blood urea nitrogen) level) at baseline and at the end of study
measure: Adverse events
time frame: 4 and 8 weeks
description: Adverse event, will be observed throughout the study conduct
arm group label: Treatment I
arm group type: Active Comparator
description: 2 Omeprazole capsules 20 mg once daily and 1 placebo caplet of DLBS2411, twice daily
arm group label: Treatment II
arm group type: Experimental
description: 1 DLBS2411 caplet 250 mg twice daily and 2 placebo capsules of Omeprazole once daily
intervention type: Drug
intervention name: Omeprazole
description: 2 Omeprazole capsules 20 mg, once daily
arm group label: Treatment I
intervention type: Drug
intervention name: Placebo caplet of DLBS2411
description: 1 placebo caplet of DLBS2411, twice daily
arm group label: Treatment I
other name: Placebo caplet of Redacid
intervention type: Drug
intervention name: DLBS2411
description: 1 DLBS2411 caplet 250 mg, twice daily
arm group label: Treatment II
other name: Redacid
intervention type: Drug
intervention name: Placebo capsule of Omeprazole
description: 2 placebo capsules of Omeprazole, once daily
arm group label: Treatment II
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: IDN Wibawa Prof. DR. Dr., SpPD-KGEH
role: Principal Investigator
affiliation: Division of Gastroenterohepatology Department of Internal Medicine Faculty of Medicine, University of Udayana Sanglah General Hospital
facility: 
country: Indonesia
responsible party type: Sponsor
mesh term: Peptic Ulcer
mesh term: Ulcer
mesh term: Omeprazole