<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/NCT01669174</url>
  </required_header>
  <id_info>
    <org_study_id>CBYM338X2204</org_study_id>
    <secondary_id>2011-000461-12</secondary_id>
    <nct_id>NCT01669174</nct_id>
  </id_info>
  <brief_title>BYM338 in Chronic Obstructive Pulmonary Disease (COPD) Patients With Cachexia</brief_title>
  <official_title>A Randomized, Double Blind, Placebo Controlled, Multi-centre Study to Asses the Pharmacodynamics, Pharmacokinetics, Safety and Tolerability of BYM338 in Chronic Obstructive Pulmonary Disease Patients With Cachexia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will assess the pharmacodynamics, pharmacokinetics, safety and tolerability of&#xD;
      BYM338 in patients with COPD and cachexia. The primary outcome will be a change in thigh&#xD;
      muscle volume compared to placebo. The study will last for approximately 24 weeks.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">December 2014</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage Change From Baseline of Thigh Muscle Volume (TMV) by MRI Scan at Week 4, 8, 16, and 24</measure>
    <time_frame>Baseline, Weeks 4, 8, 16, 24</time_frame>
    <description>Thigh Muscle Volume (TMV) change was evaluated by a responder analysis. Patients whose loss of muscle TMV by MRI was no more than or equal to 2% at Week 4,8,16 and 24 was considered responders.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in 6 Minute Walk Distance Compared to Placebo</measure>
    <time_frame>Baseline, Weeks 4, 8, 16, 24</time_frame>
    <description>Practical simple test that requires a 100-ft hallway but no exercise quipment or advanced training for technicians. Walking is an activity performed daily by all but the most severely impaired patients. This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes (the 6MWD)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Serum Concentration (Cmax)</measure>
    <time_frame>0 hour, 2 hour, Day 8, 15, 29, 57, 71, 85, 99, 113, 127, 168 post dose</time_frame>
    <description>The observed maximum plasma concentration following drug administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach the Maximum Concentration After Drug Administration (Tmax)</measure>
    <time_frame>24 weeks</time_frame>
    <description>The time to reach the maximum concentration after drug administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-56 and AUClast</measure>
    <time_frame>0 hour, 2 hour, Day 8, 15, 29, 57, 71, 85, 99, 113, 127, 168 post dose</time_frame>
    <description>AUC0-56, the area under the serum concentration-time curve from the time zero to the end of the dosing interval, day 56. AUC0-56 was analyzed for dose 1 and 2. AUClast is from time zero to the last quantifiable concentration. AUClast was analyzed for dose 2 only.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">67</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease (COPD) With Cachexia</condition>
  <arm_group>
    <arm_group_label>BYM338</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BYM338</intervention_name>
    <description>BYM338</description>
    <arm_group_label>BYM338</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Written informed consent must be obtained before any assessment is performed.&#xD;
&#xD;
          -  Males and females ages 40 to 80 years&#xD;
&#xD;
          -  Smoking history of at least 10 pack-years&#xD;
&#xD;
          -  Diagnosis of COPD according to GOLD guidelines (GOLD, 2010), with a&#xD;
             post-bronchodilator FEV¬1 &lt; 80% predicted and FEV1/FVC ratio &lt; 0.70&#xD;
&#xD;
          -  BMI &lt;20 kg/m2 or skeletal muscle mass index by DXA &lt; 7.25 kg/m2 for men or &lt;5.45 kg/m2&#xD;
             for women.&#xD;
&#xD;
          -  In general stable health, including managed COPD, by past medical history, physical&#xD;
             examination, vital signs at baseline as determined by the investigator.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Patients with MRC dyspnoea grade 5 (i.e. patients too breathless to leave the house or&#xD;
             breathless when dressing)&#xD;
&#xD;
          -  Plans for lung transplantation or lung reduction surgery within four months of&#xD;
             enrollment&#xD;
&#xD;
          -  Patients participating in a formal pulmonary rehabilitation program within 3 months of&#xD;
             dosing&#xD;
&#xD;
          -  History of malignancy of any organ system (other than excised non-melanomatous&#xD;
             carcinoma of the skin), treated or untreated, within the past 5 years, regardless of&#xD;
             whether there is evidence of local recurrence or metastases.&#xD;
&#xD;
          -  Diseases other than cancer known to cause cachexia or muscle atrophy, including but&#xD;
             not limited to congestive heart failure of any stage, chronic kidney disease&#xD;
             (estimated GFR &lt; 30 mL/min using the MDRD equation), rheumatoid arthritis, primary&#xD;
             myopathy, stroke, HIV infection, tuberculosis or other chronic infection, uncontrolled&#xD;
             diabetes mellitus, etc.&#xD;
&#xD;
          -  Inflammatory bowel disease, celiac disease, short bowel syndrome, pancreatic&#xD;
             insufficiency&#xD;
&#xD;
          -  Use of any prescription drugs known to affect muscle mass, including androgen&#xD;
             supplements, anti-androgens (such as LHRH agonists), anti-estrogens (tamoxifen, etc.)&#xD;
             recombinant human growth hormone (rhGH), insulin, oral beta agonists, megestrol&#xD;
             acetate, dronabinol, metformin, etc.&#xD;
&#xD;
          -  Hemoglobin concentration below 11.0 g/dL at screening.&#xD;
&#xD;
          -  Liver disease or liver injury.&#xD;
&#xD;
          -  Use of other investigational drugs at the time of enrollment, or within 30 days and&#xD;
             for any other limitation of participation in an investigational trial based on local&#xD;
             regulations.&#xD;
&#xD;
          -  Women of child-bearing potential.&#xD;
&#xD;
        Other protocol-defined inclusion/exclusion criteria may apply&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <zip>90502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Savannah</city>
        <state>Georgia</state>
        <zip>31419</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Normal</city>
        <state>Illinois</state>
        <zip>61761</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Missoula</city>
        <state>Montana</state>
        <zip>59808</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Spartanburg</city>
        <state>South Carolina</state>
        <zip>29303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Maastricht</city>
        <zip>6211</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Leicester</city>
        <zip>LE1 5WW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>London</city>
        <zip>SW 6NP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Machester</city>
        <zip>M23 9QZ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Romania</country>
  </removed_countries>
  <verification_date>April 2016</verification_date>
  <study_first_submitted>March 1, 2012</study_first_submitted>
  <study_first_submitted_qc>August 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2012</study_first_posted>
  <results_first_submitted>December 1, 2015</results_first_submitted>
  <results_first_submitted_qc>April 27, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">May 3, 2016</results_first_posted>
  <last_update_submitted>April 27, 2016</last_update_submitted>
  <last_update_submitted_qc>April 27, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 3, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Chronic Obstructive Pulmonary Disease</keyword>
  <keyword>COPD; cachexia; muscle wasting</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
    <mesh_term>Wasting Syndrome</mesh_term>
    <mesh_term>Cachexia</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>BYM338</title>
          <description>30 mg/kg</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo to BYM338 30mg/kg</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="33"/>
                <participants group_id="P2" count="34"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
                <participants group_id="P2" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Subject withdrew consent</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </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="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Administrative problems</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>BYM338</title>
          <description>30 mg/kg</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo to BYM338 30mg/kg</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="33"/>
            <count group_id="B2" value="34"/>
            <count group_id="B3" value="67"/>
          </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="64.5" spread="5.93"/>
                    <measurement group_id="B2" value="63.1" spread="7.51"/>
                    <measurement group_id="B3" value="63.7" spread="6.76"/>
                  </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="16"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage Change From Baseline of Thigh Muscle Volume (TMV) by MRI Scan at Week 4, 8, 16, and 24</title>
        <description>Thigh Muscle Volume (TMV) change was evaluated by a responder analysis. Patients whose loss of muscle TMV by MRI was no more than or equal to 2% at Week 4,8,16 and 24 was considered responders.</description>
        <time_frame>Baseline, Weeks 4, 8, 16, 24</time_frame>
        <population>Pharmacodynamics (PD) analysis set: Patients with evaluable PD parameter data. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame.</population>
        <group_list>
          <group group_id="O1">
            <title>BYM338</title>
            <description>30 mg/kg</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo to BYM338 30mg/kg</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage Change From Baseline of Thigh Muscle Volume (TMV) by MRI Scan at Week 4, 8, 16, and 24</title>
          <description>Thigh Muscle Volume (TMV) change was evaluated by a responder analysis. Patients whose loss of muscle TMV by MRI was no more than or equal to 2% at Week 4,8,16 and 24 was considered responders.</description>
          <population>Pharmacodynamics (PD) analysis set: Patients with evaluable PD parameter data. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame.</population>
          <units>Percentage Change of TMV</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 4 Day 29 (n=30,31)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.87" spread="3.413"/>
                    <measurement group_id="O2" value="0.02" spread="3.261"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8 Day 57 (n=27,27)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.01" spread="3.707"/>
                    <measurement group_id="O2" value="-0.65" spread="2.752"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 16 Day 113 (27,28)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.84" spread="5.052"/>
                    <measurement group_id="O2" value="-0.88" spread="4.471"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of Study, week 24 (n=27,28)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.04" spread="4.872"/>
                    <measurement group_id="O2" value="-1.31" spread="4.282"/>
                  </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>Week 4</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>106.10</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>104.64</ci_lower_limit>
            <ci_upper_limit>107.58</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Week 8</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <param_type>Median Difference (Net)</param_type>
            <param_value>107.75</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>106.18</ci_lower_limit>
            <ci_upper_limit>109.35</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Week 16</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <param_type>Median Difference (Net)</param_type>
            <param_value>108.63</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>106.31</ci_lower_limit>
            <ci_upper_limit>111.00</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Week 24</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <param_type>Median Difference (Net)</param_type>
            <param_value>106.63</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>104.39</ci_lower_limit>
            <ci_upper_limit>108.93</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in 6 Minute Walk Distance Compared to Placebo</title>
        <description>Practical simple test that requires a 100-ft hallway but no exercise quipment or advanced training for technicians. Walking is an activity performed daily by all but the most severely impaired patients. This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes (the 6MWD)</description>
        <time_frame>Baseline, Weeks 4, 8, 16, 24</time_frame>
        <population>Pharmacodynamics (PD) analysis set: Patients with evaluable PD parameter data. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame</population>
        <group_list>
          <group group_id="O1">
            <title>BYM338</title>
            <description>30 mg/kg</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo to BYM338 30mg/kg</description>
          </group>
        </group_list>
        <measure>
          <title>Change in 6 Minute Walk Distance Compared to Placebo</title>
          <description>Practical simple test that requires a 100-ft hallway but no exercise quipment or advanced training for technicians. Walking is an activity performed daily by all but the most severely impaired patients. This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes (the 6MWD)</description>
          <population>Pharmacodynamics (PD) analysis set: Patients with evaluable PD parameter data. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame</population>
          <units>meter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 4 Day 29 (n=30,32)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="364.6" spread="85.45"/>
                    <measurement group_id="O2" value="388.5" spread="100.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8 Day 57 (n=27,29)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="373.9" spread="101.42"/>
                    <measurement group_id="O2" value="387.4" spread="99.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12 Day 85 (n=27,28)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="383.0" spread="84.63"/>
                    <measurement group_id="O2" value="385.6" spread="107.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 16 Day 113 (n=25,28)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="379.7" spread="83.78"/>
                    <measurement group_id="O2" value="352.9" spread="104.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of Study week 24 (n=27, 28)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="374.9" spread="98.29"/>
                    <measurement group_id="O2" value="378.8" spread="81.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Observed Serum Concentration (Cmax)</title>
        <description>The observed maximum plasma concentration following drug administration</description>
        <time_frame>0 hour, 2 hour, Day 8, 15, 29, 57, 71, 85, 99, 113, 127, 168 post dose</time_frame>
        <population>Pharmacokinetics (PK) analysis set: Patients with evaluable PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>BYM338</title>
            <description>30 mg/kg</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Observed Serum Concentration (Cmax)</title>
          <description>The observed maximum plasma concentration following drug administration</description>
          <population>Pharmacokinetics (PK) analysis set: Patients with evaluable PK data.</population>
          <units>ug/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cmax dose 1 (n=31)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="614" spread="143"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cmax dose 2 (n=26)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="580" spread="121"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Reach the Maximum Concentration After Drug Administration (Tmax)</title>
        <description>The time to reach the maximum concentration after drug administration</description>
        <time_frame>24 weeks</time_frame>
        <population>Pharmacokinetics (PK) analysis set: Patients with evaluable PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>BYM338</title>
            <description>30 mg/kg</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Reach the Maximum Concentration After Drug Administration (Tmax)</title>
          <description>The time to reach the maximum concentration after drug administration</description>
          <population>Pharmacokinetics (PK) analysis set: Patients with evaluable PK data.</population>
          <units>hr</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tmax dose 1 (n=31)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.22" spread="NA" lower_limit="2.02" upper_limit="3.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Tmax dose 2 (n=26)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.23" spread="NA" lower_limit="1.97" upper_limit="3.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC0-56 and AUClast</title>
        <description>AUC0-56, the area under the serum concentration-time curve from the time zero to the end of the dosing interval, day 56. AUC0-56 was analyzed for dose 1 and 2. AUClast is from time zero to the last quantifiable concentration. AUClast was analyzed for dose 2 only.</description>
        <time_frame>0 hour, 2 hour, Day 8, 15, 29, 57, 71, 85, 99, 113, 127, 168 post dose</time_frame>
        <population>Pharmacokinetics (PK) analysis set: Patients with evaluable PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>BYM338</title>
            <description>30 mg/kg</description>
          </group>
        </group_list>
        <measure>
          <title>AUC0-56 and AUClast</title>
          <description>AUC0-56, the area under the serum concentration-time curve from the time zero to the end of the dosing interval, day 56. AUC0-56 was analyzed for dose 1 and 2. AUClast is from time zero to the last quantifiable concentration. AUClast was analyzed for dose 2 only.</description>
          <population>Pharmacokinetics (PK) analysis set: Patients with evaluable PK data.</population>
          <units>day*ug/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AUC0-56 dose 1 (n=26)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4540" spread="897"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AUC0-56 dose 2 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5790" spread="1300"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AUClast dose 2 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7480" spread="2080"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>BYM338 30mg/kg</title>
          <description>BYM338 30mg/kg</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo to BYM338 30mg/kg</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA</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="4" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Inguinal hernia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Postoperative wound infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Cervical vertebral fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Hip fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Road traffic accident</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Lung neoplasm malignant</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Throat cancer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Haemorrhage intracranial</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA</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="31" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="30" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Feeling abnormal</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Feeling cold</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Rash pustular</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Skin abrasion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Blood creatine phosphokinase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Blood glucose increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Haemoglobin urine present</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Urine leukocyte esterase positive</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Joint lock</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="26" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Muscle tightness</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Muscle twitching</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Musculoskeletal stiffness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Dyspnoea exertional</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Blister</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Ecchymosis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Papule</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Petechiae</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Skin exfoliation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Haematoma</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="33"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
              </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>The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Novartis Pharmaceuticals</organization>
      <phone>862-778-8300</phone>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01669174
org study id: CBYM338X2204
secondary id: 2011-000461-12
nct id: NCT01669174
lead sponsor: 
has dmc: Yes
This study will assess the pharmacodynamics, pharmacokinetics, safety and tolerability of
      BYM338 in patients with COPD and cachexia. The primary outcome will be a change in thigh
      muscle volume compared to placebo. The study will last for approximately 24 weeks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Percentage Change From Baseline of Thigh Muscle Volume (TMV) by MRI Scan at Week 4, 8, 16, and 24
time frame: Baseline, Weeks 4, 8, 16, 24
description: Thigh Muscle Volume (TMV) change was evaluated by a responder analysis. Patients whose loss of muscle TMV by MRI was no more than or equal to 2% at Week 4,8,16 and 24 was considered responders.
measure: Change in 6 Minute Walk Distance Compared to Placebo
time frame: Baseline, Weeks 4, 8, 16, 24
description: Practical simple test that requires a 100-ft hallway but no exercise quipment or advanced training for technicians. Walking is an activity performed daily by all but the most severely impaired patients. This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes (the 6MWD)
measure: Maximum Observed Serum Concentration (Cmax)
time frame: 0 hour, 2 hour, Day 8, 15, 29, 57, 71, 85, 99, 113, 127, 168 post dose
description: The observed maximum plasma concentration following drug administration
measure: Time to Reach the Maximum Concentration After Drug Administration (Tmax)
time frame: 24 weeks
description: The time to reach the maximum concentration after drug administration
measure: AUC0-56 and AUClast
time frame: 0 hour, 2 hour, Day 8, 15, 29, 57, 71, 85, 99, 113, 127, 168 post dose
description: AUC0-56, the area under the serum concentration-time curve from the time zero to the end of the dosing interval, day 56. AUC0-56 was analyzed for dose 1 and 2. AUClast is from time zero to the last quantifiable concentration. AUClast was analyzed for dose 2 only.
arm group label: BYM338
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
intervention type: Drug
intervention name: BYM338
description: BYM338
arm group label: BYM338
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Netherlands
country: United Kingdom
country: United States
country: Romania
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Wasting Syndrome
mesh term: Cachexia
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 