<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/NCT02257489</url>
  </required_header>
  <id_info>
    <org_study_id>A083-01</org_study_id>
    <nct_id>NCT02257489</nct_id>
  </id_info>
  <brief_title>Phase 1 Study of ACE-083 in Healthy Subjects</brief_title>
  <official_title>A Phase 1, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects of Local Muscle Injections of ACE-083 in Healthy Postmenopausal Women</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck &amp; Co., Inc., Rahway, NJ USA</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck &amp; Co., Inc., Rahway, NJ USA</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate the safety and tolerability of single and multiple doses of ACE-083&#xD;
      as a local injection into selected skeletal muscles of healthy subjects. The study will also&#xD;
      determine the amount of ACE-083 that reaches the systemic circulation following local&#xD;
      administration. Additionally, the study will assess whether local administration into&#xD;
      skeletal muscle results in an increase in the size and/or strength of the injected muscle.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      ACE-083 is a molecule that has been shown to increase skeletal muscle mass in animals and,&#xD;
      therefore, has potential utility in certain diseases that affect skeletal muscle. This&#xD;
      initial study in healthy human subjects will help determine the properties of ACE-083&#xD;
      (safety, tolerability, drug absorption and biologic activity), following local administration&#xD;
      into skeletal muscle, in advance of clinical trials in patients.&#xD;
&#xD;
      The study will consist of up to 7 planned groups of 8 or 9 subjects each. Subjects in each&#xD;
      cohort will be randomized to receive either ACE-083 or placebo. ACE-083 (or placebo) will be&#xD;
      administered locally into the right quadriceps (thigh) muscle or right tibialis anterior&#xD;
      (lower leg) muscle. Subjects will receive a total of either one dose (on Day 1) or two doses&#xD;
      (on Day 1 and Day 22). Each dose administered could include up to 4 injections of study drug&#xD;
      into pre-defined locations in the muscle.&#xD;
&#xD;
      A Safety Review Team (SRT) will review blinded, preliminary data from each treatment group to&#xD;
      make recommendations regarding escalation to the next treatment group. Subjects will be&#xD;
      assessed for safety throughout the treatment and follow-up periods. Follow-up visits will&#xD;
      occur over 12 weeks following the last dose of study drug.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">April 2016</completion_date>
  <primary_completion_date type="Actual">March 2016</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>ACE-083 Safety and Tolerability: Number of Subjects With Adverse Events</measure>
    <time_frame>From initiation of treatment (Study Day 1) to end of follow up period (up to Study Day 106)</time_frame>
    <description>Safety/tolerability assessment, following intramuscular administration, includes adverse events, injection site reactions, laboratory measurements, vital signs, etc.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>ACE-083 Pharmacokinetics: Maximum Measured Plasma Concentrations</measure>
    <time_frame>PK samples were collected predose, and at 3 hours and 6 hours postdose.</time_frame>
    <description>Assessment of systemic absorption and exposure following local injection of ACE-083 into the thigh or lower leg muscle</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ACE-083 Pharmacodynamics</measure>
    <time_frame>From initiation of treatment (Study Day 1) to end of follow up period (up to Study Day 106)</time_frame>
    <description>Pharmacodynamic assessments include measurements of thigh or lower leg volume and composition (by MRI) and muscle strength testing (by hand-held dynamometer and fixed system)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ACE-083 Pharmacokinetics: Time of the Maximum Measured Plasma Concentration</measure>
    <time_frame>PK samples were collected predose, and at 3 hours and 6 hours postdose.</time_frame>
    <description>Assessment of systemic absorption and exposure following local injection of ACE-083 into the thigh or lower leg muscle</description>
  </secondary_outcome>
  <number_of_arms>7</number_of_arms>
  <enrollment type="Actual">58</enrollment>
  <condition>Musculoskeletal Diseases</condition>
  <arm_group>
    <arm_group_label>50 mg single dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>8 subjects in total; 6 subjects to received ACE-083 (50 mg) and 2 subjects to receive placebo, single injection, intramuscularly</description>
  </arm_group>
  <arm_group>
    <arm_group_label>100 mg single dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>8 subjects in total; 6 subjects to received ACE-083 (100 mg) and 2 subjects to receive placebo, single injection, intramuscularly</description>
  </arm_group>
  <arm_group>
    <arm_group_label>200 mg single dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>8 subjects in total; 6 subjects to received ACE-083 (200 mg) and 2 subjects to receive placebo, single injection, intramuscularly</description>
  </arm_group>
  <arm_group>
    <arm_group_label>100 mg multiple dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>8 subjects in total; 6 subjects to received ACE-083 (100 mg) and 2 subjects to receive placebo, two injections 3 weeks apart, intramuscularly</description>
  </arm_group>
  <arm_group>
    <arm_group_label>200 mg multiple dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>8 subjects in total; 6 subjects to received ACE-083 (200 mg) and 2 subjects to receive placebo, two injections 3 weeks apart, intramuscularly</description>
  </arm_group>
  <arm_group>
    <arm_group_label>100 mg (multiple dose)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>9 subjects in total; 6 subjects to received ACE-083 (100 mg) and 3 subjects to receive placebo, two injections 3 weeks apart, intramuscularly</description>
  </arm_group>
  <arm_group>
    <arm_group_label>150 mg multiple dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>9 subjects in total; 6 subjects to received ACE-083 (150 mg) and 3 subjects to receive placebo, two injections 3 weeks apart, intramuscularly</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ACE-083</intervention_name>
    <description>recombinant fusion protein</description>
    <arm_group_label>100 mg (multiple dose)</arm_group_label>
    <arm_group_label>100 mg multiple dose</arm_group_label>
    <arm_group_label>100 mg single dose</arm_group_label>
    <arm_group_label>150 mg multiple dose</arm_group_label>
    <arm_group_label>200 mg multiple dose</arm_group_label>
    <arm_group_label>200 mg single dose</arm_group_label>
    <arm_group_label>50 mg single dose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Postmenopausal women, defined by follicle stimulating hormone (FSH) level &gt; 40 IU/L&#xD;
             and either 12 months of spontaneous amenorrhea or at least 6 months post-surgical&#xD;
             bilateral oophorectomy and/or hysterectomy&#xD;
&#xD;
          -  BMI 18.5-32 kg/m2&#xD;
&#xD;
          -  Clinical laboratory values that meet the following criteria prior to dosing on Study&#xD;
             Day 1: (i) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2 x&#xD;
             upper limit of normal (ULN), (ii) Calculated creatinine clearance ≥ 60 mL/min, (iii)&#xD;
             Platelet count ≥ 100 x109/L&#xD;
&#xD;
          -  Able to adhere to the study visit schedule, understand and comply with protocol&#xD;
             requirements&#xD;
&#xD;
          -  Understand and sign written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of hepatitis B (HBsAg and HB core Ab), human immunodeficiency virus (HIV)&#xD;
             antibody or active hepatitis C&#xD;
&#xD;
          -  Positive drug or alcohol screen test at screening or on Day 1&#xD;
&#xD;
          -  History of drug or alcohol abuse (as defined by the Investigator) or required&#xD;
             treatment for drug or alcohol use within 2 years of Day 1&#xD;
&#xD;
          -  Donation or loss ≥ 500 mL of whole blood within 2 months prior to Day 1&#xD;
&#xD;
          -  History of opportunistic infection (e.g., invasive candidiasis or pneumocystis&#xD;
             pneumonia) within 6 months prior to screening; serious local infection (e.g.,&#xD;
             cellulitis, abscess) or systemic infection (e.g., septicemia) within 3 months prior to&#xD;
             screening&#xD;
&#xD;
          -  History of severe allergic or anaphylactic reaction or hypersensitivity to recombinant&#xD;
             proteins&#xD;
&#xD;
          -  History of active malignancy, with the exception of fully excised or treated basal&#xD;
             cell carcinoma, cervical carcinoma in-situ, or ≤ 2 squamous cell carcinomas of the&#xD;
             skin&#xD;
&#xD;
          -  History of clinically significant (as determined by the Investigator) cardiac,&#xD;
             endocrine, hematologic, hepatic, immune, metabolic, urologic, pulmonary, neurologic,&#xD;
             neuromuscular, dermatologic, psychiatric, renal, and/or other disease&#xD;
&#xD;
          -  Treatment with systemic glucocorticoid therapy, statin medication, insulin, oral&#xD;
             hormone replacement therapy or any other therapy (including investigational) with&#xD;
             known or intended effects on muscle within 3 months prior to Day 1&#xD;
&#xD;
          -  Treatment with anti-platelet, anti-coagulant, or any other therapy (including&#xD;
             investigational) with known or intended effects on bleeding risk within 1 week prior&#xD;
             to Day 1&#xD;
&#xD;
          -  Treatment with another investigational drug, or approved therapy for investigational&#xD;
             use within 4 weeks prior to Day 1, or if the half-life of the previous product is&#xD;
             known, within 5 times the half-life prior to Day 1, whichever is longer&#xD;
&#xD;
          -  Treatment within 3 months prior to Day 1 with any potent cytochrome P450 (CYP) 3A4/5&#xD;
             inhibitors (e.g., verapamil, ketoconazole, micronazole, itraconazole, erythromycin,&#xD;
             telithromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir,&#xD;
             lopinavir, atazanavir, amprenavir, fosamprenavir, delavirdine) or CYP3A4/5 inducers&#xD;
             (carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin,&#xD;
             amobarbital, nevirapine, primidone, rifabutin, rifampin, St. John's wort)&#xD;
&#xD;
          -  Subject is unwilling or unable to maintain physical activity at baseline level for the&#xD;
             duration of the study&#xD;
&#xD;
          -  Subject has any condition that would prevent MRI scanning (e.g., pacemaker, knee/hip&#xD;
             replacement, metallic implant, or extreme claustrophobia)&#xD;
&#xD;
          -  Subject is unsuitable for enrollment in the opinion of the Investigator or Sponsor for&#xD;
             other unspecified reasons&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trials Manager</last_name>
    <role>Study Director</role>
    <affiliation>Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck &amp; Co., Inc., Rahway, NJ USA</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Acceleron Investigative Site</name>
      <address>
        <city>Lincoln</city>
        <state>Nebraska</state>
        <zip>68502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>October 2, 2014</study_first_submitted>
  <study_first_submitted_qc>October 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 6, 2014</study_first_posted>
  <results_first_submitted>October 30, 2018</results_first_submitted>
  <results_first_submitted_qc>April 19, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">July 8, 2019</results_first_posted>
  <last_update_submitted>September 12, 2022</last_update_submitted>
  <last_update_submitted_qc>September 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 23, 2022</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>Musculoskeletal Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>50 mg Single Dose (RF)</title>
          <description>8 subjects in total; 6 subjects to receive ACE-083 (50 mg) and 2 subjects to receive placebo, single injection, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
        </group>
        <group group_id="P2">
          <title>100 mg Single Dose (RF)</title>
          <description>8 subjects in total; 6 subjects to receive ACE-083 (100 mg) and 2 subjects to receive placebo, single injection, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
        </group>
        <group group_id="P3">
          <title>200 mg Single Dose (RF)</title>
          <description>8 subjects in total; 6 subjects to receive ACE-083 (200 mg) and 2 subjects to receive placebo, single injection, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
        </group>
        <group group_id="P4">
          <title>100 mg Multiple Dose (RF)</title>
          <description>8 subjects in total; 6 subjects to receive ACE-083 (100 mg) and 2 subjects to receive placebo, two injections 3 weeks apart, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
        </group>
        <group group_id="P5">
          <title>200 mg Multiple Dose (RF)</title>
          <description>8 subjects in total; 6 subjects to receive ACE-083 (200 mg) and 2 subjects to receive placebo, two injections 3 weeks apart, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
        </group>
        <group group_id="P6">
          <title>100 mg Multiple Dose (TA)</title>
          <description>9 subjects in total; 6 subjects to receive ACE-083 (100 mg) and 3 subjects to receive placebo, two injections 3 weeks apart, intramuscularly in the tibialis anterior (TA)&#xD;
ACE-083: recombinant fusion protein</description>
        </group>
        <group group_id="P7">
          <title>150 mg Multiple Dose (TA)</title>
          <description>9 subjects in total; 6 subjects to receive ACE-083 (150 mg) and 3 subjects to receive placebo, two injections 3 weeks apart, intramuscularly in the tibialis anterior (TA)&#xD;
ACE-083: recombinant fusion protein</description>
        </group>
        <group group_id="P8">
          <title>Pooled Placebo (RF)</title>
          <description>Pooled placebo from the rectus femoris (RF) cohorts, n=10 (n=2 from each RF cohort)</description>
        </group>
        <group group_id="P9">
          <title>Pooled Placebo (TA)</title>
          <description>Pooled placebo from the tibialis anterior cohorts, n=6 (n=3 from each TA cohort)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="6"/>
                <participants group_id="P6" count="6"/>
                <participants group_id="P7" count="6"/>
                <participants group_id="P8" count="10"/>
                <participants group_id="P9" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="5"/>
                <participants group_id="P5" count="6"/>
                <participants group_id="P6" count="6"/>
                <participants group_id="P7" count="6"/>
                <participants group_id="P8" count="10"/>
                <participants group_id="P9" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>50 mg Single Dose (RF)</title>
          <description>8 subjects in total; 6 subjects to receive ACE-083 (50 mg) and 2 subjects to receive placebo, single injection, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
        </group>
        <group group_id="B2">
          <title>100 mg Single Dose (RF)</title>
          <description>8 subjects in total; 6 subjects to receive ACE-083 (100 mg) and 2 subjects to receive placebo, single injection, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
        </group>
        <group group_id="B3">
          <title>200 mg Single Dose (RF)</title>
          <description>8 subjects in total; 6 subjects to receive ACE-083 (200 mg) and 2 subjects to receive placebo, single injection, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
        </group>
        <group group_id="B4">
          <title>100 mg Multiple Dose (RF)</title>
          <description>8 subjects in total; 6 subjects to receive ACE-083 (100 mg) and 2 subjects to receive placebo, two injections 3 weeks apart, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
        </group>
        <group group_id="B5">
          <title>200 mg Multiple Dose (RF)</title>
          <description>8 subjects in total; 6 subjects to receive ACE-083 (200 mg) and 2 subjects to receive placebo, two injections 3 weeks apart, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
        </group>
        <group group_id="B6">
          <title>100 mg Multiple Dose (TA)</title>
          <description>9 subjects in total; 6 subjects to receive ACE-083 (100 mg) and 3 subjects to receive placebo, two injections 3 weeks apart, intramuscularly in the tibialis anterior (TA)&#xD;
ACE-083: recombinant fusion protein</description>
        </group>
        <group group_id="B7">
          <title>150 mg Multiple Dose (TA)</title>
          <description>9 subjects in total; 6 subjects to receive ACE-083 (150 mg) and 3 subjects to receive placebo, two injections 3 weeks apart, intramuscularly in the tibialis anterior (TA)&#xD;
ACE-083: recombinant fusion protein</description>
        </group>
        <group group_id="B8">
          <title>Pooled Placebo (RF)</title>
          <description>Pooled placebo from the rectus femoris (RF) cohorts, n=10 (n=2 from each RF cohort)</description>
        </group>
        <group group_id="B9">
          <title>Pooled Placebo (TA)</title>
          <description>Pooled placebo from the tibialis anterior cohorts, n=6 (n=3 from each TA cohort)</description>
        </group>
        <group group_id="B10">
          <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="6"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="6"/>
            <count group_id="B4" value="6"/>
            <count group_id="B5" value="6"/>
            <count group_id="B6" value="6"/>
            <count group_id="B7" value="6"/>
            <count group_id="B8" value="10"/>
            <count group_id="B9" value="6"/>
            <count group_id="B10" value="58"/>
          </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="58.0" spread="4.29"/>
                    <measurement group_id="B2" value="54.2" spread="9.99"/>
                    <measurement group_id="B3" value="55.0" spread="2.37"/>
                    <measurement group_id="B4" value="55.2" spread="3.71"/>
                    <measurement group_id="B5" value="57.0" spread="2.45"/>
                    <measurement group_id="B6" value="55.7" spread="3.08"/>
                    <measurement group_id="B7" value="57.0" spread="4.73"/>
                    <measurement group_id="B8" value="59.2" spread="5.53"/>
                    <measurement group_id="B9" value="56.7" spread="7.50"/>
                    <measurement group_id="B10" value="56.6" spread="5.2"/>
                  </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="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="6"/>
                    <measurement group_id="B6" value="6"/>
                    <measurement group_id="B7" value="6"/>
                    <measurement group_id="B8" value="10"/>
                    <measurement group_id="B9" value="6"/>
                    <measurement group_id="B10" value="58"/>
                  </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 group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                    <measurement group_id="B10" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                    <measurement group_id="B10" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="6"/>
                    <measurement group_id="B6" value="5"/>
                    <measurement group_id="B7" value="6"/>
                    <measurement group_id="B8" value="10"/>
                    <measurement group_id="B9" value="6"/>
                    <measurement group_id="B10" value="55"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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 group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                    <measurement group_id="B10" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</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 group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                    <measurement group_id="B10" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</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 group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                    <measurement group_id="B10" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</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 group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                    <measurement group_id="B10" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</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="1"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="1"/>
                    <measurement group_id="B10" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="6"/>
                    <measurement group_id="B6" value="6"/>
                    <measurement group_id="B7" value="6"/>
                    <measurement group_id="B8" value="10"/>
                    <measurement group_id="B9" value="5"/>
                    <measurement group_id="B10" value="56"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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 group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                    <measurement group_id="B10" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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 group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                    <measurement group_id="B10" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>ACE-083 Safety and Tolerability: Number of Subjects With Adverse Events</title>
        <description>Safety/tolerability assessment, following intramuscular administration, includes adverse events, injection site reactions, laboratory measurements, vital signs, etc.</description>
        <time_frame>From initiation of treatment (Study Day 1) to end of follow up period (up to Study Day 106)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>50 mg Single Dose (RF)</title>
            <description>8 subjects in total; 6 subjects to receive ACE-083 (50 mg) and 2 subjects to receive placebo, single injection, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
          </group>
          <group group_id="O2">
            <title>100 mg Single Dose (RF)</title>
            <description>8 subjects in total; 6 subjects to receive ACE-083 (100 mg) and 2 subjects to receive placebo, single injection, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
          </group>
          <group group_id="O3">
            <title>200 mg Single Dose (RF)</title>
            <description>8 subjects in total; 6 subjects to receive ACE-083 (200 mg) and 2 subjects to receive placebo, single injection, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
          </group>
          <group group_id="O4">
            <title>100 mg Multiple Dose (RF)</title>
            <description>8 subjects in total; 6 subjects to receive ACE-083 (100 mg) and 2 subjects to receive placebo, two injections 3 weeks apart, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
          </group>
          <group group_id="O5">
            <title>200 mg Multiple Dose (RF)</title>
            <description>8 subjects in total; 6 subjects to receive ACE-083 (200 mg) and 2 subjects to receive placebo, two injections 3 weeks apart, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
          </group>
          <group group_id="O6">
            <title>100 mg Multiple Dose (TA)</title>
            <description>9 subjects in total; 6 subjects to receive ACE-083 (100 mg) and 3 subjects to receive placebo, two injections 3 weeks apart, intramuscularly in the tibialis anterior (TA)&#xD;
ACE-083: recombinant fusion protein</description>
          </group>
          <group group_id="O7">
            <title>150 mg Multiple Dose (TA)</title>
            <description>9 subjects in total; 6 subjects to receive ACE-083 (150 mg) and 3 subjects to receive placebo, two injections 3 weeks apart, intramuscularly in the tibialis anterior (TA)&#xD;
ACE-083: recombinant fusion protein</description>
          </group>
          <group group_id="O8">
            <title>Pooled Placebo (RF)</title>
            <description>Pooled placebo from the rectus femoris (RF) cohorts, n=10 (n=2 from each RF cohort)</description>
          </group>
          <group group_id="O9">
            <title>Pooled Placebo (TA)</title>
            <description>Pooled placebo from the tibialis anterior cohorts, n=6 (n=3 from each TA cohort)</description>
          </group>
        </group_list>
        <measure>
          <title>ACE-083 Safety and Tolerability: Number of Subjects With Adverse Events</title>
          <description>Safety/tolerability assessment, following intramuscular administration, includes adverse events, injection site reactions, laboratory measurements, vital signs, etc.</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="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="6"/>
                <count group_id="O7" value="6"/>
                <count group_id="O8" value="10"/>
                <count group_id="O9" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="6"/>
                    <measurement group_id="O4" value="6"/>
                    <measurement group_id="O5" value="6"/>
                    <measurement group_id="O6" value="6"/>
                    <measurement group_id="O7" value="6"/>
                    <measurement group_id="O8" value="10"/>
                    <measurement group_id="O9" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>ACE-083 Pharmacokinetics: Maximum Measured Plasma Concentrations</title>
        <description>Assessment of systemic absorption and exposure following local injection of ACE-083 into the thigh or lower leg muscle</description>
        <time_frame>PK samples were collected predose, and at 3 hours and 6 hours postdose.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>50 mg Single Dose (RF)</title>
            <description>8 subjects in total; 6 subjects to receive ACE-083 (50 mg) and 2 subjects to receive placebo, single injection, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
          </group>
          <group group_id="O2">
            <title>100 mg Single Dose (RF)</title>
            <description>8 subjects in total; 6 subjects to receive ACE-083 (100 mg) and 2 subjects to receive placebo, single injection, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
          </group>
          <group group_id="O3">
            <title>200 mg Single Dose (RF)</title>
            <description>8 subjects in total; 6 subjects to receive ACE-083 (200 mg) and 2 subjects to receive placebo, single injection, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
          </group>
          <group group_id="O4">
            <title>100 mg Multiple Dose (RF)</title>
            <description>8 subjects in total; 6 subjects to receive ACE-083 (100 mg) and 2 subjects to receive placebo, two injections 3 weeks apart, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
          </group>
          <group group_id="O5">
            <title>200 mg Multiple Dose (RF)</title>
            <description>8 subjects in total; 6 subjects to receive ACE-083 (200 mg) and 2 subjects to receive placebo, two injections 3 weeks apart, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
          </group>
          <group group_id="O6">
            <title>100 mg Multiple Dose (TA)</title>
            <description>9 subjects in total; 6 subjects to receive ACE-083 (100 mg) and 3 subjects to receive placebo, two injections 3 weeks apart, intramuscularly in the tibialis anterior (TA)&#xD;
ACE-083: recombinant fusion protein</description>
          </group>
          <group group_id="O7">
            <title>150 mg Multiple Dose (TA)</title>
            <description>9 subjects in total; 6 subjects to receive ACE-083 (150 mg) and 3 subjects to receive placebo, two injections 3 weeks apart, intramuscularly in the tibialis anterior (TA)&#xD;
ACE-083: recombinant fusion protein</description>
          </group>
        </group_list>
        <measure>
          <title>ACE-083 Pharmacokinetics: Maximum Measured Plasma Concentrations</title>
          <description>Assessment of systemic absorption and exposure following local injection of ACE-083 into the thigh or lower leg muscle</description>
          <units>ng/mL (Cmax)</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="6"/>
                <count group_id="O7" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cmax (min) dose 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                    <measurement group_id="O7" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cmax (max) dose 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="168"/>
                    <measurement group_id="O3" value="226"/>
                    <measurement group_id="O4" value="112"/>
                    <measurement group_id="O5" value="219"/>
                    <measurement group_id="O6" value="132"/>
                    <measurement group_id="O7" value="136"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>ACE-083 Pharmacodynamics</title>
        <description>Pharmacodynamic assessments include measurements of thigh or lower leg volume and composition (by MRI) and muscle strength testing (by hand-held dynamometer and fixed system)</description>
        <time_frame>From initiation of treatment (Study Day 1) to end of follow up period (up to Study Day 106)</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>ACE-083 Pharmacokinetics: Time of the Maximum Measured Plasma Concentration</title>
        <description>Assessment of systemic absorption and exposure following local injection of ACE-083 into the thigh or lower leg muscle</description>
        <time_frame>PK samples were collected predose, and at 3 hours and 6 hours postdose.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>50 mg Single Dose (RF)</title>
            <description>8 subjects in total; 6 subjects to receive ACE-083 (50 mg) and 2 subjects to receive placebo, single injection, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
          </group>
          <group group_id="O2">
            <title>100 mg Single Dose (RF)</title>
            <description>8 subjects in total; 6 subjects to receive ACE-083 (100 mg) and 2 subjects to receive placebo, single injection, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
          </group>
          <group group_id="O3">
            <title>200 mg Single Dose (RF)</title>
            <description>8 subjects in total; 6 subjects to receive ACE-083 (200 mg) and 2 subjects to receive placebo, single injection, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
          </group>
          <group group_id="O4">
            <title>100 mg Multiple Dose (RF)</title>
            <description>8 subjects in total; 6 subjects to receive ACE-083 (100 mg) and 2 subjects to receive placebo, two injections 3 weeks apart, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
          </group>
          <group group_id="O5">
            <title>200 mg Multiple Dose (RF)</title>
            <description>8 subjects in total; 6 subjects to receive ACE-083 (200 mg) and 2 subjects to receive placebo, two injections 3 weeks apart, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
          </group>
          <group group_id="O6">
            <title>100 mg Multiple Dose (TA)</title>
            <description>9 subjects in total; 6 subjects to receive ACE-083 (100 mg) and 3 subjects to receive placebo, two injections 3 weeks apart, intramuscularly in the tibialis anterior (TA)&#xD;
ACE-083: recombinant fusion protein</description>
          </group>
          <group group_id="O7">
            <title>150 mg Multiple Dose (TA)</title>
            <description>9 subjects in total; 6 subjects to receive ACE-083 (150 mg) and 3 subjects to receive placebo, two injections 3 weeks apart, intramuscularly in the tibialis anterior (TA)&#xD;
ACE-083: recombinant fusion protein</description>
          </group>
        </group_list>
        <measure>
          <title>ACE-083 Pharmacokinetics: Time of the Maximum Measured Plasma Concentration</title>
          <description>Assessment of systemic absorption and exposure following local injection of ACE-083 into the thigh or lower leg muscle</description>
          <units>h (Tmax)</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="6"/>
                <count group_id="O6" value="6"/>
                <count group_id="O7" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tmax (min) dose 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="96"/>
                    <measurement group_id="O3" value="96"/>
                    <measurement group_id="O4" value="96"/>
                    <measurement group_id="O5" value="600"/>
                    <measurement group_id="O6" value="24.00"/>
                    <measurement group_id="O7" value="96.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Tmax (max) dose 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="96"/>
                    <measurement group_id="O3" value="168"/>
                    <measurement group_id="O4" value="96"/>
                    <measurement group_id="O5" value="600"/>
                    <measurement group_id="O6" value="96.0"/>
                    <measurement group_id="O7" value="96.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>50 mg Single Dose (RF)</title>
          <description>8 subjects in total; 6 subjects to receive ACE-083 (50 mg) and 2 subjects to receive placebo, single injection, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
        </group>
        <group group_id="E2">
          <title>100 mg Single Dose (RF)</title>
          <description>8 subjects in total; 6 subjects to receive ACE-083 (100 mg) and 2 subjects to receive placebo, single injection, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
        </group>
        <group group_id="E3">
          <title>200 mg Single Dose (RF)</title>
          <description>8 subjects in total; 6 subjects to receive ACE-083 (200 mg) and 2 subjects to receive placebo, single injection, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
        </group>
        <group group_id="E4">
          <title>100 mg Multiple Dose (RF)</title>
          <description>8 subjects in total; 6 subjects to receive ACE-083 (100 mg) and 2 subjects to receive placebo, two injections 3 weeks apart, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
        </group>
        <group group_id="E5">
          <title>200 mg Multiple Dose (RF)</title>
          <description>8 subjects in total; 6 subjects to receive ACE-083 (200 mg) and 2 subjects to receive placebo, two injections 3 weeks apart, intramuscularly in the rectus femoris (RF)&#xD;
ACE-083: recombinant fusion protein</description>
        </group>
        <group group_id="E6">
          <title>100 mg Multiple Dose (TA)</title>
          <description>9 subjects in total; 6 subjects to receive ACE-083 (100 mg) and 3 subjects to receive placebo, two injections 3 weeks apart, intramuscularly in the tibialis anterior (TA)&#xD;
ACE-083: recombinant fusion protein</description>
        </group>
        <group group_id="E7">
          <title>150 mg Multiple Dose (TA)</title>
          <description>9 subjects in total; 6 subjects to receive ACE-083 (150 mg) and 3 subjects to receive placebo, two injections 3 weeks apart, intramuscularly in the tibialis anterior (TA)&#xD;
ACE-083: recombinant fusion protein</description>
        </group>
        <group group_id="E8">
          <title>Pooled Placebo (RF)</title>
          <description>Pooled placebo from the rectus femoris (RF) cohorts, n=10 (n=2 from each RF cohort)</description>
        </group>
        <group group_id="E9">
          <title>Pooled Placebo (TA)</title>
          <description>Pooled placebo from the tibialis anterior cohorts, n=6 (n=3 from each TA cohort)</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </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="6" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="10" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="6" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Ear discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Eye irritation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Gingival pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Injection site pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="10" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="6" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Injection site haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Injection site reaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Injection site discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Injection site erythema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Injection site warmth</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Injection site hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Injection site paresthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Injection site oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Injection site pruritus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Local swelling</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Feeling hot</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Oral herpes</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Arthropod bite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Ligament sprain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Nerve injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Increased appetite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle twitching</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="5" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Musculoskeletal stiffness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Joint stiffness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Limb discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Muscle tightness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Muscle fatigue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Groin pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Migraine</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Sinus headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Sensory disturbance</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Aphonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Breast tenderness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus congestion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Throat irritation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract congestion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dry throat</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Sneezing</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Generalised erythema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Skin odour abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Skin tightness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="6"/>
              </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>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Senior Vice President, Global Clinical Development</name_or_title>
      <organization>Merck Sharp &amp; Dohme LLC</organization>
      <phone>1-800-672-6372</phone>
      <email>ClinicalTrialsDisclosure@merck.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02257489
org study id: A083-01
nct id: NCT02257489
lead sponsor: 
has dmc: No
This study will evaluate the safety and tolerability of single and multiple doses of ACE-083
      as a local injection into selected skeletal muscles of healthy subjects. The study will also
      determine the amount of ACE-083 that reaches the systemic circulation following local
      administration. Additionally, the study will assess whether local administration into
      skeletal muscle results in an increase in the size and/or strength of the injected muscle.
ACE-083 is a molecule that has been shown to increase skeletal muscle mass in animals and,
      therefore, has potential utility in certain diseases that affect skeletal muscle. This
      initial study in healthy human subjects will help determine the properties of ACE-083
      (safety, tolerability, drug absorption and biologic activity), following local administration
      into skeletal muscle, in advance of clinical trials in patients.

      The study will consist of up to 7 planned groups of 8 or 9 subjects each. Subjects in each
      cohort will be randomized to receive either ACE-083 or placebo. ACE-083 (or placebo) will be
      administered locally into the right quadriceps (thigh) muscle or right tibialis anterior
      (lower leg) muscle. Subjects will receive a total of either one dose (on Day 1) or two doses
      (on Day 1 and Day 22). Each dose administered could include up to 4 injections of study drug
      into pre-defined locations in the muscle.

      A Safety Review Team (SRT) will review blinded, preliminary data from each treatment group to
      make recommendations regarding escalation to the next treatment group. Subjects will be
      assessed for safety throughout the treatment and follow-up periods. Follow-up visits will
      occur over 12 weeks following the last dose of study drug.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: ACE-083 Safety and Tolerability: Number of Subjects With Adverse Events
time frame: From initiation of treatment (Study Day 1) to end of follow up period (up to Study Day 106)
description: Safety/tolerability assessment, following intramuscular administration, includes adverse events, injection site reactions, laboratory measurements, vital signs, etc.
measure: ACE-083 Pharmacokinetics: Maximum Measured Plasma Concentrations
time frame: PK samples were collected predose, and at 3 hours and 6 hours postdose.
description: Assessment of systemic absorption and exposure following local injection of ACE-083 into the thigh or lower leg muscle
measure: ACE-083 Pharmacodynamics
time frame: From initiation of treatment (Study Day 1) to end of follow up period (up to Study Day 106)
description: Pharmacodynamic assessments include measurements of thigh or lower leg volume and composition (by MRI) and muscle strength testing (by hand-held dynamometer and fixed system)
measure: ACE-083 Pharmacokinetics: Time of the Maximum Measured Plasma Concentration
time frame: PK samples were collected predose, and at 3 hours and 6 hours postdose.
description: Assessment of systemic absorption and exposure following local injection of ACE-083 into the thigh or lower leg muscle
arm group label: 50 mg single dose
arm group type: Experimental
description: 8 subjects in total; 6 subjects to received ACE-083 (50 mg) and 2 subjects to receive placebo, single injection, intramuscularly
arm group label: 100 mg single dose
arm group type: Experimental
description: 8 subjects in total; 6 subjects to received ACE-083 (100 mg) and 2 subjects to receive placebo, single injection, intramuscularly
arm group label: 200 mg single dose
arm group type: Experimental
description: 8 subjects in total; 6 subjects to received ACE-083 (200 mg) and 2 subjects to receive placebo, single injection, intramuscularly
arm group label: 100 mg multiple dose
arm group type: Experimental
description: 8 subjects in total; 6 subjects to received ACE-083 (100 mg) and 2 subjects to receive placebo, two injections 3 weeks apart, intramuscularly
arm group label: 200 mg multiple dose
arm group type: Experimental
description: 8 subjects in total; 6 subjects to received ACE-083 (200 mg) and 2 subjects to receive placebo, two injections 3 weeks apart, intramuscularly
arm group label: 100 mg (multiple dose)
arm group type: Experimental
description: 9 subjects in total; 6 subjects to received ACE-083 (100 mg) and 3 subjects to receive placebo, two injections 3 weeks apart, intramuscularly
arm group label: 150 mg multiple dose
arm group type: Experimental
description: 9 subjects in total; 6 subjects to received ACE-083 (150 mg) and 3 subjects to receive placebo, two injections 3 weeks apart, intramuscularly
intervention type: Drug
intervention name: ACE-083
description: recombinant fusion protein
arm group label: 100 mg (multiple dose)
arm group label: 100 mg multiple dose
arm group label: 100 mg single dose
arm group label: 150 mg multiple dose
arm group label: 200 mg multiple dose
arm group label: 200 mg single dose
arm group label: 50 mg single dose
criteria: 
gender: Female
minimum age: 45 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Clinical Trials Manager
role: Study Director
affiliation: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
facility: 
country: United States
responsible party type: Sponsor
mesh term: Musculoskeletal Diseases
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 