<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/NCT01701193</url>
  </required_header>
  <id_info>
    <org_study_id>Ade002</org_study_id>
    <nct_id>NCT01701193</nct_id>
    <nct_alias>NCT04250467</nct_alias>
  </id_info>
  <brief_title>A Clinical Study of Alanyl-Glutamine for Reduction of Post-Myomectomy Adhesions</brief_title>
  <official_title>A Randomized Double-Blind Controlled Proof-of-Concept Study of Alanyl-Glutamine for Reduction of Post-Myomectomy Adhesions</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Temple Therapeutics BV</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Temple Therapeutics BV</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates whether L-Alanyl-L-Glutamine can reduce the incidence, extent and&#xD;
      severity of adhesions after myomectomy. Half of the participants will receive&#xD;
      L-Alanyl-L-Glutamine and the other half of participants will receive a saline placebo at the&#xD;
      time of myomectomy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The myriad medical and financial burdens of post-operative adhesions are well documented;&#xD;
      however, treatment options are limited and controversial. Implantable physical barriers to&#xD;
      prevent adhesions are commercially available, but most trials have failed to demonstrate&#xD;
      compelling evidence to support widespread use. In recent years, advances have been made in&#xD;
      our understanding of the cellular mechanisms underlying adhesiogenesis, raising the prospect&#xD;
      of targeting these pathways to prevent post-surgical adhesions. However, to date, no drug has&#xD;
      received regulatory approval for this purpose in any jurisdiction. Our study was designed to&#xD;
      evaluate the efficacy and safety of a single intraoperative intraperitoneal dose of&#xD;
      L-Alanyl-L-Glutamine (AG), an agent which has been shown to act upon key mediators in the&#xD;
      adhesion formation pathway.&#xD;
&#xD;
      Methods: This was a randomized, double-blind, placebo-controlled study (DBRCT) of 47 women&#xD;
      who underwent myomectomies by laparoscopy (N=37; AG-18 vs Placebo-19) or laparotomy (N=10;&#xD;
      AG-5 vs Placebo-5) with a scheduled clinically necessary second-look laparoscopy (SLL) 6 - 8&#xD;
      weeks later. Digital recordings were obtained for all procedures. The primary endpoint was&#xD;
      reduction in the incidence, severity and extent of post-operative adhesions, as analyzed by&#xD;
      intention-to-treat (ITT) approach.&#xD;
&#xD;
      Three independent, blinded reviewers evaluated the operative video recordings to assess for&#xD;
      presence of adhesions. Secondary endpoints assessed the safety and tolerability of AG.&#xD;
      Post-hoc analysis assessed presence or absence of adhesions in the peritoneal cavity.&#xD;
      Patients included those with previous history of surgery, endometriosis, and adhesiolysis was&#xD;
      permitted at myomectomy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 15, 2015</start_date>
  <completion_date type="Actual">October 20, 2016</completion_date>
  <primary_completion_date type="Actual">October 20, 2016</primary_completion_date>
  <phase>Phase 1/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>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants in Which Adhesions Were Prevented.</measure>
    <time_frame>6-8 weeks</time_frame>
    <description>The American Fertility Society (AFS) grading system for adhesions was used to assess incidence of adhesions. Adhesion prevention was determined through grading of adhesions at the time of myomectomy (initial surgery) and at the time of second look surgery and compared.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse Events, Adverse Drug Reactions and Clinical Laboratory Abnormalities.</measure>
    <time_frame>8 weeks</time_frame>
    <description>Participants With Treatment-related Adverse Events as Assessed by Clinical Blood Work Abnormalities and Physical Examination.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>Pelvic Adhesions</condition>
  <arm_group>
    <arm_group_label>Physiological saline- Laparoscopic</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants receiving intraperitoneal administration of physiological saline at the time of laparoscopic myomectomy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>L-Alanyl/L-Glutamine- Laparoscopic</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receiving intraperitoneal administration of L-Alanyl-L-Glutamine at the time of laparoscopic myomectomy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Physiological saline- Laparotomy</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants receiving intraperitoneal administration of physiological saline at the time of myomectomy (laparotomy).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>L-Alanyl/L-Glutamine- Laparotomy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receiving intraperitoneal administration of L-Alanyl-L-Glutamine at the time of myomectomy (laparotomy).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>L-Alanyl/L-Glutamine</intervention_name>
    <description>Sterile solution of L-Alanyl-L-Glutamine, 400mg/mL in water for injection. It is dosed at 1g/kg of body weight and is instilled into the peritoneum at the time of surgery. The active ingredient, glutamine, is a conditionally essential amino acid component of nutritional supplements.</description>
    <arm_group_label>L-Alanyl/L-Glutamine- Laparoscopic</arm_group_label>
    <arm_group_label>L-Alanyl/L-Glutamine- Laparotomy</arm_group_label>
    <other_name>Evitar</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Physiologic saline</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Physiological saline- Laparoscopic</arm_group_label>
    <arm_group_label>Physiological saline- Laparotomy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects are female&#xD;
&#xD;
          -  Subjects are 18 years of age or older at the time of consent&#xD;
&#xD;
          -  Subjects have a BMI between 17-40&#xD;
&#xD;
          -  Subjects must have signed informed consent form&#xD;
&#xD;
          -  Subjects have a preoperative diagnosis of uterine fibroids and plan to have a&#xD;
             myomectomy completed surgically as part of their standard of care&#xD;
&#xD;
          -  Subjects must have a physical examination and compliance assessment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects whose BMI is outside the range of 17-40&#xD;
&#xD;
          -  Subjects participating in another clinical trial with a drug or device&#xD;
&#xD;
          -  Subjects who have participated in a clinical trial with a drug or device within 30&#xD;
             days prior to this study&#xD;
&#xD;
          -  Subjects with suspected or diagnosed pregnancy&#xD;
&#xD;
          -  Subjects with suspected intraabdominal infection&#xD;
&#xD;
          -  Subjects who are immunocompromised&#xD;
&#xD;
          -  Subjects diagnosed with cancer&#xD;
&#xD;
          -  Subjects treated with hemostatic agents (e.g. fibrin sealant, collagen, oxidized&#xD;
             cellulose)&#xD;
&#xD;
          -  Subjects treated with adhesion prevention agents other than the Anti-Adhesion product&#xD;
             (APP) (e.g. Intergel ® Adhesion Prevention Solution, Seprafilm ® Membrane)&#xD;
&#xD;
          -  Subjects taking anti-epileptic medication&#xD;
&#xD;
          -  Subjects who have been treated with Methotrexate or other chemotherapeutics agents&#xD;
&#xD;
          -  Subjects with an American Fertility Society score of Stage D at the time of myomectomy&#xD;
             as determined by the surgeon&#xD;
&#xD;
          -  Positive viral serology screening results for hepatitis B surface antigen, antibodies&#xD;
             to hepatitis C virus or human immunodeficiency&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Donna Chizen, MD, FRCSC</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Saskatchewan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>8Surgery and Endoscopy Department of Kharkiv Medical Academy of Postgraduate Education Kharkiv City Clinical Multi-field Hospital</name>
      <address>
        <city>Kharkiv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Ukraine</country>
  </location_countries>
  <removed_countries>
    <country>Canada</country>
  </removed_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>October 3, 2012</study_first_submitted>
  <study_first_submitted_qc>October 3, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 5, 2012</study_first_posted>
  <results_first_submitted>January 27, 2021</results_first_submitted>
  <results_first_submitted_qc>April 14, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">May 7, 2021</results_first_posted>
  <last_update_submitted>April 14, 2021</last_update_submitted>
  <last_update_submitted_qc>April 14, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 7, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tissue Adhesions</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This was a single-center study at a private hospital clinic. Recruitment was between February 2015 and October 2016. Subjects were adult women planned for myomectomy with a scheduled clinically necessary second look laparoscopy. The study and consent form were approved by the Institutional Review Board/Ethics Committee and the Investigator's IRB/EC (Ethics Committee of Kharkiv City Clinical Multi-field Hospital,Kharkiv, Ukraine). Participants were not compensated to participate in this trial.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>L-Alanyl/L-Glutamine- Laparoscopic</title>
          <description>Participants receiving intraperitoneal administration of L-Alanyl-L-Glutamine at the time of laparoscopic myomectomy.&#xD;
L-Alanyl/L-Glutamine: Sterile solution of L-Alanyl-L-Glutamine, 400mg/mL in water for injection. It is dosed at 1g/kg of body weight and is instilled into the peritoneum at the time of surgery. The active ingredient, glutamine, is a conditionally essential amino acid component of nutritional supplements.</description>
        </group>
        <group group_id="P2">
          <title>Physiological Saline- Laparoscopic</title>
          <description>Participants receiving intraperitoneal administration of physiological saline at the time of laparoscopic myomectomy.&#xD;
Physiologic saline: Placebo</description>
        </group>
        <group group_id="P3">
          <title>L-Alanyl/L-Glutamine- Laparotomy</title>
          <description>Participants receiving intraperitoneal administration of L-Alanyl-L-Glutamine at the time of myomectomy (laparotomy).</description>
        </group>
        <group group_id="P4">
          <title>Physiological Saline- Laparotomy</title>
          <description>Participants receiving intraperitoneal administration of physiological saline at the time of myomectomy (laparotomy).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="19"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="17"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>L-Alanyl/L-Glutamine- Laparoscopic</title>
          <description>Participants receiving intraperitoneal administration of L-Alanyl-L-Glutamine at the time of laparoscopic myomectomy.&#xD;
L-Alanyl/L-Glutamine: Sterile solution of L-Alanyl-L-Glutamine, 400mg/mL in water for injection. It is dosed at 1g/kg of body weight and is instilled into the peritoneum at the time of surgery. The active ingredient, glutamine, is a conditionally essential amino acid component of nutritional supplements.</description>
        </group>
        <group group_id="B2">
          <title>Physiological Saline- Laparoscopic</title>
          <description>Participants receiving intraperitoneal administration of physiological saline at the time of laparoscopic myomectomy.&#xD;
Physiologic saline: Placebo</description>
        </group>
        <group group_id="B3">
          <title>L-Alanyl/L-Glutamine- Laparotomy</title>
          <description>Participants receiving intraperitoneal administration of L-Alanyl-L-Glutamine at the time of myomectomy (laparotomy).&#xD;
L-Alanyl/L-Glutamine: Sterile solution of L-Alanyl-L-Glutamine, 400mg/mL in water for injection. It is dosed at 1g/kg of body weight and is instilled into the peritoneum at the time of surgery. The active ingredient, glutamine, is a conditionally essential amino acid component of nutritional supplements.</description>
        </group>
        <group group_id="B4">
          <title>Physiological Saline- Laparotomy</title>
          <description>Participants receiving intraperitoneal administration of physiological saline at the time of myomectomy (laparotomy).&#xD;
Physiologic saline: Placebo</description>
        </group>
        <group group_id="B5">
          <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="18"/>
            <count group_id="B2" value="19"/>
            <count group_id="B3" value="5"/>
            <count group_id="B4" value="5"/>
            <count group_id="B5" value="47"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="18"/>
                    <count group_id="B2" value="19"/>
                    <count group_id="B3" value="5"/>
                    <count group_id="B4" value="5"/>
                    <count group_id="B5" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="47"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="18"/>
                    <count group_id="B2" value="19"/>
                    <count group_id="B3" value="5"/>
                    <count group_id="B4" value="5"/>
                    <count group_id="B5" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="47"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="0"/>
                    <count group_id="B5" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI (kg/m^2)</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="18"/>
                    <count group_id="B2" value="19"/>
                    <count group_id="B3" value="5"/>
                    <count group_id="B4" value="5"/>
                    <count group_id="B5" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23.5" spread="4.3"/>
                    <measurement group_id="B2" value="22.3" spread="3.0"/>
                    <measurement group_id="B3" value="24.5" spread="7.9"/>
                    <measurement group_id="B4" value="23.5" spread="3.5"/>
                    <measurement group_id="B5" value="23.5" spread="0.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Temperature (Degrees Celsius)</title>
          <units>Degrees Celsius</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="18"/>
                    <count group_id="B2" value="19"/>
                    <count group_id="B3" value="5"/>
                    <count group_id="B4" value="5"/>
                    <count group_id="B5" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="36.7" spread="0.1"/>
                    <measurement group_id="B2" value="36.3" spread="0.1"/>
                    <measurement group_id="B3" value="36.7" spread="0.1"/>
                    <measurement group_id="B4" value="36.6" spread="0.1"/>
                    <measurement group_id="B5" value="36.5" spread="0.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Heart rate (bpm)</title>
          <units>beats per minute</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="18"/>
                    <count group_id="B2" value="19"/>
                    <count group_id="B3" value="5"/>
                    <count group_id="B4" value="5"/>
                    <count group_id="B5" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="79.8" spread="8.6"/>
                    <measurement group_id="B2" value="79.4" spread="7.6"/>
                    <measurement group_id="B3" value="79" spread="1.8"/>
                    <measurement group_id="B4" value="73" spread="8.3"/>
                    <measurement group_id="B5" value="77.8" spread="3.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Systolic BP (mmHg)</title>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="18"/>
                    <count group_id="B2" value="19"/>
                    <count group_id="B3" value="5"/>
                    <count group_id="B4" value="5"/>
                    <count group_id="B5" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="113.9" spread="9.5"/>
                    <measurement group_id="B2" value="113.9" spread="8.6"/>
                    <measurement group_id="B3" value="117" spread="5.7"/>
                    <measurement group_id="B4" value="110" spread="10"/>
                    <measurement group_id="B5" value="113.7" spread="2.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Diastolic BP (mmHg)</title>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="18"/>
                    <count group_id="B2" value="19"/>
                    <count group_id="B3" value="5"/>
                    <count group_id="B4" value="5"/>
                    <count group_id="B5" value="47"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="70.0" spread="5.0"/>
                    <measurement group_id="B2" value="70.3" spread="6.1"/>
                    <measurement group_id="B3" value="71" spread="2.2"/>
                    <measurement group_id="B4" value="67" spread="6.7"/>
                    <measurement group_id="B5" value="69.6" spread="1.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants in Which Adhesions Were Prevented.</title>
        <description>The American Fertility Society (AFS) grading system for adhesions was used to assess incidence of adhesions. Adhesion prevention was determined through grading of adhesions at the time of myomectomy (initial surgery) and at the time of second look surgery and compared.</description>
        <time_frame>6-8 weeks</time_frame>
        <population>The number of subjects in each study group (Control [N=20] and AG [N=19]) was lower at the second look laparoscopic (SLL) compared to the number of subjects originally enrolled in each study group. The difference between groups numbers is a result of dropouts, including subjects who failed criteria for SLL or who elected not to continue the study. The laparotomy group, given the small sample size, was primary used to gather safety data.</population>
        <group_list>
          <group group_id="O1">
            <title>L-Alanyl/L-Glutamine- Laparoscopic</title>
            <description>Participants receiving intraperitoneal administration of L-Alanyl-L-Glutamine at the time of laparoscopic myomectomy.&#xD;
L-Alanyl/L-Glutamine: Sterile solution of L-Alanyl-L-Glutamine, 400mg/mL in water for injection. It is dosed at 1g/kg of body weight and is instilled into the peritoneum at the time of surgery. The active ingredient, glutamine, is a conditionally essential amino acid component of nutritional supplements.</description>
          </group>
          <group group_id="O2">
            <title>Physiological Saline- Laparoscopic</title>
            <description>Participants receiving intraperitoneal administration of physiological saline at the time of laparoscopic myomectomy.&#xD;
Physiologic saline: Placebo</description>
          </group>
          <group group_id="O3">
            <title>L-Alanyl/L-Glutamine- Laparotomy</title>
            <description>Participants receiving intraperitoneal administration of L-Alanyl-L-Glutamine at the time of myomectomy (laparotomy).&#xD;
L-Alanyl/L-Glutamine: Sterile solution of L-Alanyl-L-Glutamine, 400mg/mL in water for injection. It is dosed at 1g/kg of body weight and is instilled into the peritoneum at the time of surgery. The active ingredient, glutamine, is a conditionally essential amino acid component of nutritional supplements.</description>
          </group>
          <group group_id="O4">
            <title>Physiological Saline- Laparotomy</title>
            <description>Participants receiving intraperitoneal administration of physiological saline at the time of myomectomy (laparotomy).&#xD;
Physiologic saline: Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants in Which Adhesions Were Prevented.</title>
          <description>The American Fertility Society (AFS) grading system for adhesions was used to assess incidence of adhesions. Adhesion prevention was determined through grading of adhesions at the time of myomectomy (initial surgery) and at the time of second look surgery and compared.</description>
          <population>The number of subjects in each study group (Control [N=20] and AG [N=19]) was lower at the second look laparoscopic (SLL) compared to the number of subjects originally enrolled in each study group. The difference between groups numbers is a result of dropouts, including subjects who failed criteria for SLL or who elected not to continue the study. The laparotomy group, given the small sample size, was primary used to gather safety data.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="17"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="4"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Adverse Events, Adverse Drug Reactions and Clinical Laboratory Abnormalities.</title>
        <description>Participants With Treatment-related Adverse Events as Assessed by Clinical Blood Work Abnormalities and Physical Examination.</description>
        <time_frame>8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>L-Alanyl/L-Glutamine</title>
            <description>Participants receiving intraperitoneal administration of L-Alanyl-L-Glutamine at the time of laparoscopic myomectomy.&#xD;
L-Alanyl/L-Glutamine: Sterile solution of L-Alanyl-L-Glutamine, 400mg/mL in water for injection. It is dosed at 1g/kg of body weight and is instilled into the peritoneum at the time of surgery. The active ingredient, glutamine, is a conditionally essential amino acid component of nutritional supplements.</description>
          </group>
          <group group_id="O2">
            <title>Physiological Saline</title>
            <description>Participants receiving intraperitoneal administration of physiological saline at the time of laparoscopic myomectomy.&#xD;
Physiologic saline: Placebo</description>
          </group>
          <group group_id="O3">
            <title>L-Alanyl/L-Glutamine- Laparotomy</title>
            <description>Participants receiving intraperitoneal administration of L-Alanyl-L-Glutamine at the time of myomectomy (laparotomy).&#xD;
L-Alanyl/L-Glutamine: Sterile solution of L-Alanyl-L-Glutamine, 400mg/mL in water for injection. It is dosed at 1g/kg of body weight and is instilled into the peritoneum at the time of surgery. The active ingredient, glutamine, is a conditionally essential amino acid component of nutritional supplements.</description>
          </group>
          <group group_id="O4">
            <title>Physiological Saline- Laparotomy</title>
            <description>Participants receiving intraperitoneal administration of physiological saline at the time of myomectomy (laparotomy)&#xD;
Physiologic saline: Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Adverse Events, Adverse Drug Reactions and Clinical Laboratory Abnormalities.</title>
          <description>Participants With Treatment-related Adverse Events as Assessed by Clinical Blood Work Abnormalities and Physical Examination.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="19"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were monitored for 8 weeks post-myomectomy.</time_frame>
      <desc>Safety was assessed though the incidence of adverse drug events (AE) and clinical lab abnormalities. The laparotomy arms were included for safety analysis, and laboratory assessments were conducted at the time of myomectomy and at SLL for all patients that enrolled and completed the study.</desc>
      <group_list>
        <group group_id="E1">
          <title>L-Alanyl/L-Glutamine- Laparoscopic</title>
          <description>Participants receiving intraperitoneal administration of L-Alanyl-L-Glutamine at the time of laparoscopic myomectomy.&#xD;
L-Alanyl/L-Glutamine: Sterile solution of L-Alanyl-L-Glutamine, 400mg/mL in water for injection. It is dosed at 1g/kg of body weight and is instilled into the peritoneum at the time of surgery. The active ingredient, glutamine, is a conditionally essential amino acid component of nutritional supplements.</description>
        </group>
        <group group_id="E2">
          <title>Physiological Saline- Laparoscopic</title>
          <description>Participants receiving intraperitoneal administration of physiological saline at the time of laparoscopic myomectomy.&#xD;
Physiologic saline: Placebo</description>
        </group>
        <group group_id="E3">
          <title>L-Alanyl/L-Glutamine- Laparotomy</title>
          <description>Participants receiving intraperitoneal administration of L-Alanyl-L-Glutamine at the time of myomectomy (laparotomy).&#xD;
L-Alanyl/L-Glutamine: Sterile solution of L-Alanyl-L-Glutamine, 400mg/mL in water for injection. It is dosed at 1g/kg of body weight and is instilled into the peritoneum at the time of surgery. The active ingredient, glutamine, is a conditionally essential amino acid component of nutritional supplements.</description>
        </group>
        <group group_id="E4">
          <title>Physiological Saline -Laparotomy</title>
          <description>Participants receiving intraperitoneal administration of physiological saline at the time of myomectomy (laparotomy).&#xD;
Physiologic saline: Placebo</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="19"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Elevated AST levels</sub_title>
                <description>aspartate aminotransferase (AST)</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Elevated temperature</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Elevated CPK levels</sub_title>
                <description>creatine phosphokinase (CPK)</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </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 NOT 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>
    <limitations_and_caveats>There were no limitations and caveats to the trial that would impact the integrity, analysis or interpretation of the trial results. Dropouts were accounted for in the study design and those excluded did not impact the statistics and/or the power of the trial.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Roger Pierson, PhD</name_or_title>
      <organization>University of Saskatchewan</organization>
      <phone>306-884-1059</phone>
      <email>roger.pierson@usask.ca</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/NCT01701193
org study id: Ade002
nct id: NCT01701193
nct alias: NCT04250467
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study evaluates whether L-Alanyl-L-Glutamine can reduce the incidence, extent and
      severity of adhesions after myomectomy. Half of the participants will receive
      L-Alanyl-L-Glutamine and the other half of participants will receive a saline placebo at the
      time of myomectomy.
The myriad medical and financial burdens of post-operative adhesions are well documented;
      however, treatment options are limited and controversial. Implantable physical barriers to
      prevent adhesions are commercially available, but most trials have failed to demonstrate
      compelling evidence to support widespread use. In recent years, advances have been made in
      our understanding of the cellular mechanisms underlying adhesiogenesis, raising the prospect
      of targeting these pathways to prevent post-surgical adhesions. However, to date, no drug has
      received regulatory approval for this purpose in any jurisdiction. Our study was designed to
      evaluate the efficacy and safety of a single intraoperative intraperitoneal dose of
      L-Alanyl-L-Glutamine (AG), an agent which has been shown to act upon key mediators in the
      adhesion formation pathway.

      Methods: This was a randomized, double-blind, placebo-controlled study (DBRCT) of 47 women
      who underwent myomectomies by laparoscopy (N=37; AG-18 vs Placebo-19) or laparotomy (N=10;
      AG-5 vs Placebo-5) with a scheduled clinically necessary second-look laparoscopy (SLL) 6 - 8
      weeks later. Digital recordings were obtained for all procedures. The primary endpoint was
      reduction in the incidence, severity and extent of post-operative adhesions, as analyzed by
      intention-to-treat (ITT) approach.

      Three independent, blinded reviewers evaluated the operative video recordings to assess for
      presence of adhesions. Secondary endpoints assessed the safety and tolerability of AG.
      Post-hoc analysis assessed presence or absence of adhesions in the peritoneal cavity.
      Patients included those with previous history of surgery, endometriosis, and adhesiolysis was
      permitted at myomectomy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of Participants in Which Adhesions Were Prevented.
time frame: 6-8 weeks
description: The American Fertility Society (AFS) grading system for adhesions was used to assess incidence of adhesions. Adhesion prevention was determined through grading of adhesions at the time of myomectomy (initial surgery) and at the time of second look surgery and compared.
measure: Adverse Events, Adverse Drug Reactions and Clinical Laboratory Abnormalities.
time frame: 8 weeks
description: Participants With Treatment-related Adverse Events as Assessed by Clinical Blood Work Abnormalities and Physical Examination.
arm group label: Physiological saline- Laparoscopic
arm group type: Placebo Comparator
description: Participants receiving intraperitoneal administration of physiological saline at the time of laparoscopic myomectomy.
arm group label: L-Alanyl/L-Glutamine- Laparoscopic
arm group type: Experimental
description: Participants receiving intraperitoneal administration of L-Alanyl-L-Glutamine at the time of laparoscopic myomectomy.
arm group label: Physiological saline- Laparotomy
arm group type: Placebo Comparator
description: Participants receiving intraperitoneal administration of physiological saline at the time of myomectomy (laparotomy).
arm group label: L-Alanyl/L-Glutamine- Laparotomy
arm group type: Experimental
description: Participants receiving intraperitoneal administration of L-Alanyl-L-Glutamine at the time of myomectomy (laparotomy).
intervention type: Drug
intervention name: L-Alanyl/L-Glutamine
description: Sterile solution of L-Alanyl-L-Glutamine, 400mg/mL in water for injection. It is dosed at 1g/kg of body weight and is instilled into the peritoneum at the time of surgery. The active ingredient, glutamine, is a conditionally essential amino acid component of nutritional supplements.
arm group label: L-Alanyl/L-Glutamine- Laparoscopic
arm group label: L-Alanyl/L-Glutamine- Laparotomy
other name: Evitar
intervention type: Drug
intervention name: Physiologic saline
description: Placebo
arm group label: Physiological saline- Laparoscopic
arm group label: Physiological saline- Laparotomy
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Donna Chizen, MD, FRCSC
role: Principal Investigator
affiliation: University of Saskatchewan
facility: 
country: Ukraine
country: Canada
responsible party type: Sponsor
mesh term: Tissue Adhesions
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: There were no limitations and caveats to the trial that would impact the integrity, analysis or interpretation of the trial results. Dropouts were accounted for in the study design and those excluded did not impact the statistics and/or the power of the trial.
point of contact: 