<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/NCT02207946</url>
  </required_header>
  <id_info>
    <org_study_id>MRZ60201_2094_1</org_study_id>
    <nct_id>NCT02207946</nct_id>
  </id_info>
  <brief_title>Botulinum Toxin A to Treat Arm Tremor</brief_title>
  <official_title>Prospective, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of the Efficacy and Safety of NT 201 in the Unilateral Treatment of Essential Tremor of the Upper Limb</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merz Pharmaceuticals GmbH</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Merz Pharmaceuticals GmbH</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this study is to assess the efficacy and safety of a single,&#xD;
      kinematic-analysis-based intramuscular injection of NT 201, compared with placebo, in&#xD;
      moderate to marked essential tremor of the upper limb.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 5, 2014</start_date>
  <completion_date type="Actual">September 26, 2016</completion_date>
  <primary_completion_date type="Actual">May 9, 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline to Week 4 in Maximum Angular Tremor Amplitude of the Wrist (Injected Limb)</measure>
    <time_frame>Baseline up to Week 4</time_frame>
    <description>No primary efficacy variables are defined for this study. One of the secondary outcome measures is used for CTgov protocol registration and results reporting purposes only. TremorTek is a tremor kinematic analytics investigational device which is used to measure maximum angular tremor amplitude at wrist of the injected limb (unit: degrees). Angular tremor amplitude is the measure of tremor severity. Reduction of angular tremor amplitude at wrist of the injected limb represents tremor improvement.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 4 in Maximum Log-transformed Accelerometric Tremor Amplitude at Wrist Level (Injected Limb)</measure>
    <time_frame>Baseline up to Week 4</time_frame>
    <description>TremorTek is a tremor kinematic analytics investigational device which is used to measure maximum log-transformed accelerometric tremor amplitude at wrist level of the injected limb (unit: meter per square second [m/s˄2]). Log-transformed accelerometric tremor amplitude is a measure of tremor severity reflecting the non-vectoral intensity of tremor. Reduction of log-transformed accelerometric tremor amplitude at wrist level of the injected limb represents a tremor improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 4 in Fahn-Tolosa-Marin (FTM) Tremor Score in Injected Limb (Item 5 [Right Upper Extremity] or 6 [Left Upper Extremity])</measure>
    <time_frame>Baseline up to Week 4</time_frame>
    <description>The FTM tremor rating scale is used for evaluation of tremor severity and function and consists of three parts (A, B, C). For this outcome measure the score of FTM scale item 5 (&quot;right upper extremity&quot;) or item 6 (&quot;left upper extremity&quot;) is used (both items are from part A). The outcome values are calculated as the sum of the three functions &quot;at rest&quot;, &quot;with posture holding&quot;, and &quot;with action and intention&quot;. The score for each item ranges from 0 (normal) to 4 (severe), that is, the possible values range from 0 to 12.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 4 in FTM Motor Performance Score (Items 11-15)</measure>
    <time_frame>Baseline up to Week 4</time_frame>
    <description>The FTM tremor rating scale was used for evaluation of tremor severity and function. This investigator-assessed scale consists of 3 parts (A, B and C). Part A: Tremor location/Severity rating (items 1-10); Part B: Specific motor tasks / Function rating (items 11-15). Ratings for five motor tasks (handwriting, drawing [large/small spiral, line], and pouring); and Part C: Functional disabilities resulting from tremor/activities of daily living (items 16-23). For this outcome measure, the sum of the five FTM motor performance items (from Part B) were used: item 11 ('handwriting for dominant hand only' - irrespective of its injection or non-injection), items 12 to 15 ('drawing large and small spiral', 'line drawing', 'pouring' for the injected upper limb). The score for each item ranges from 0 (normal) to 4 (severe). Possible values range for total FTM motor performance score: 0-20.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participant's Global Impression of Change Scale (GICS) at Week 4</measure>
    <time_frame>Week 4</time_frame>
    <description>The GICS was used to measure the participant's impression of change due to treatment. The response option was a common 7-point Likert scale, with the following values: +3 (very much improved); +2 (much improved); +1 (minimally improved); 0 (no change); -1 (minimally worse); -2 (much worse); -3 (very much worse).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Investigator's Global Impression of Change Scale (GICS) at Week 4</measure>
    <time_frame>Week 4</time_frame>
    <description>The GICS was used to measure the investigator's impression of change due to treatment. The response option was a common 7-point Likert scale, with the following values: +3 (very much improved); +2 (much improved); +1 (minimally improved); 0 (no change); -1 (minimally worse); -2 (much worse); -3 (very much worse).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Essential Tremor of the Upper Limbs</condition>
  <arm_group>
    <arm_group_label>200 Units incobotulinumtoxinA (Xeomin)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single injection cycle, total dose of up to 200 Units, intramuscular injection into muscles of wrist (mandatory) and shoulder and/or elbow (both optional).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Single injection cycle, intramuscular injection into muscles of wrist (mandatory) and shoulder and/or elbow (both optional).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IncobotulinumtoxinA</intervention_name>
    <description>Active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).</description>
    <arm_group_label>200 Units incobotulinumtoxinA (Xeomin)</arm_group_label>
    <other_name>Xeomin</other_name>
    <other_name>NT 201</other_name>
    <other_name>Botulinum toxin type A (150 kiloDalton), free from complexing proteins</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Main Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of 'definite essential tremor' in accordance with modified TRIG criteria, as&#xD;
             follows:&#xD;
&#xD;
               -  Bilateral postural tremor with or without kinetic tremor, involving hands and&#xD;
                  forearms, that is visible and persistent.&#xD;
&#xD;
               -  It is to be noted that:&#xD;
&#xD;
               -  Tremor of other body parts may be present in addition to upper limb tremor.&#xD;
&#xD;
               -  Bilateral tremor may be asymmetric.&#xD;
&#xD;
               -  Tremor is reported by patient to be persistent, although the amplitude may&#xD;
                  fluctuate.&#xD;
&#xD;
          -  First onset of essential tremor at least 6 months before screening with stability of&#xD;
             the tremor symptoms over 4 weeks and in the opinion of the investigator definite&#xD;
             diagnosis of essential tremor.&#xD;
&#xD;
          -  Moderate-to-marked upper-limb postural and/or kinetic tremor at wrist level,&#xD;
             corresponding to Fahn-Tolosa-Marin upper-limb tremor rating of at least 2 categories&#xD;
             (scale part C, items 16-23) in the limb to be treated between of 2 or higher.&#xD;
&#xD;
          -  Visible tremor at wrist level in at least one of the four positions/tasks used in&#xD;
             kinematic assessments&#xD;
&#xD;
          -  Tremor deemed by the investigator to require a treatment with 30 - 200 U NT 201 for a&#xD;
             treatment of up to three joints of the selected upper limb (wrist treatment&#xD;
             mandatory).&#xD;
&#xD;
          -  Stable concomitant anti-tremor medication and no clinically relevant findings in&#xD;
             routine laboratory examinations.&#xD;
&#xD;
        Main Exclusion Criteria:&#xD;
&#xD;
          -  Any neurological signs abnormal for the subject's age, other than the tremor itself&#xD;
             and Froment's maneuver.&#xD;
&#xD;
          -  Exposure to the following tremorogenic drugs: Lithium, Valproic acid, Amiodarone,&#xD;
             typical and atypical neuroleptics. Exposure to other than the listed tremorogenic or&#xD;
             potentially tremorogenic drugs is allowed only if, in the opinion of the investigator,&#xD;
             this will not interfere with the study drug evaluation. In these cases, a stable&#xD;
             medication should be reached 4 weeks before screening and intended for the time during&#xD;
             the study drug evaluation.&#xD;
&#xD;
          -  Trauma to the central nervous system or the nerves of the target limb within the three&#xD;
             months preceding the onset of tremor.&#xD;
&#xD;
          -  Evidence of psychogenic origins of tremor.&#xD;
&#xD;
          -  Life habits (e.g. smoking, alcohol or substance abuse) prejudicial to study&#xD;
             participation.&#xD;
&#xD;
          -  Prior surgery to treat tremor&#xD;
&#xD;
          -  Recent (16 weeks) treatment with any Botulinum toxin product for any reason.&#xD;
&#xD;
          -  Relevant recent or planned surgery or other specified relevant treatments and/or&#xD;
             concomitant disorders.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Merz Medical Expert</last_name>
    <role>Study Director</role>
    <affiliation>Merz Pharmaceuticals GmbH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Merz Investigational Site #0010191</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Merz Investigational Site #0010317</name>
      <address>
        <city>Winnipeg</city>
        <state>Manitoba</state>
        <zip>R3J2H7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Merz Investigational Site #0010089</name>
      <address>
        <city>Halifax</city>
        <state>Nova Scotia</state>
        <zip>B3P 1M3</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Merz Investigational Site #0010078</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5T 2S8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Merz Investigational Site #0010305/1</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M6M 2J5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Merz Investigational Site #0010305/2</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M6M 2J5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Jog M, Lee J, Scheschonka A, Chen R, Ismail F, Boulias C, Hobson D, King D, Althaus M, Simon O, Dersch H, Frucht S, Simpson DM. Tolerability and Efficacy of Customized IncobotulinumtoxinA Injections for Essential Tremor: A Randomized, Double-Blind, Placebo-Controlled Study. Toxins (Basel). 2020 Dec 20;12(12):807. doi: 10.3390/toxins12120807.</citation>
    <PMID>33419261</PMID>
  </results_reference>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>August 1, 2014</study_first_submitted>
  <study_first_submitted_qc>August 1, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 4, 2014</study_first_posted>
  <results_first_submitted>January 20, 2021</results_first_submitted>
  <results_first_submitted_qc>February 11, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">February 18, 2021</results_first_posted>
  <disposition_first_submitted>April 26, 2017</disposition_first_submitted>
  <disposition_first_submitted_qc>April 26, 2017</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">April 27, 2017</disposition_first_posted>
  <last_update_submitted>February 11, 2021</last_update_submitted>
  <last_update_submitted_qc>February 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 18, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tremor</mesh_term>
    <mesh_term>Essential Tremor</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Botulinum Toxins</mesh_term>
    <mesh_term>Botulinum Toxins, Type A</mesh_term>
    <mesh_term>abobotulinumtoxinA</mesh_term>
    <mesh_term>incobotulinumtoxinA</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The multicenter study was conducted at 6 investigational sites in the United States and Canada.</recruitment_details>
      <pre_assignment_details>A total of 52 participants were screened, out of which 30 participants were randomized and treated.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>IncobotulinumtoxinA 30 to 200 Units</title>
          <description>Participants received incobotulinumtoxinA (also known as NT 201) between 30 to 200 units (U), powder for solution for injection, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Participants received placebo solution matched to the volume of incobotulinumtoxinA solution, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA placebo.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The safety evaluation set (SES) was the subset of all participants who received study medication (incobotulinumtoxinA or placebo) at least once.</population>
      <group_list>
        <group group_id="B1">
          <title>IncobotulinumtoxinA 30 to 200 U</title>
          <description>Participants received incobotulinumtoxinA (also known as NT 201) between 30 to 200 U, powder for solution for injection, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Participants received placebo solution matched to the volume of incobotulinumtoxinA solution, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA placebo.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="19"/>
            <count group_id="B2" value="11"/>
            <count group_id="B3" value="30"/>
          </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="68.1" spread="10.6"/>
                    <measurement group_id="B2" value="68.2" spread="10.2"/>
                    <measurement group_id="B3" value="68.1" spread="10.3"/>
                  </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="10"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>American Indian or Alaska Native</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Native Hawaiian or Other Pacific Islander</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline to Week 4 in Maximum Angular Tremor Amplitude of the Wrist (Injected Limb)</title>
        <description>No primary efficacy variables are defined for this study. One of the secondary outcome measures is used for CTgov protocol registration and results reporting purposes only. TremorTek is a tremor kinematic analytics investigational device which is used to measure maximum angular tremor amplitude at wrist of the injected limb (unit: degrees). Angular tremor amplitude is the measure of tremor severity. Reduction of angular tremor amplitude at wrist of the injected limb represents tremor improvement.</description>
        <time_frame>Baseline up to Week 4</time_frame>
        <population>The full analysis set (FAS) was defined as the subset of participants who received study medication (incobotulinumtoxinA or placebo) at least once, and for whom a post-baseline value of any efficacy variable was measured.</population>
        <group_list>
          <group group_id="O1">
            <title>IncobotulinumtoxinA 30 to 200 U</title>
            <description>Participants received incobotulinumtoxinA (also known as NT 201) between 30 to 200 units (U), powder for solution for injection, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo solution matched to the volume of incobotulinumtoxinA solution, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA placebo.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 4 in Maximum Angular Tremor Amplitude of the Wrist (Injected Limb)</title>
          <description>No primary efficacy variables are defined for this study. One of the secondary outcome measures is used for CTgov protocol registration and results reporting purposes only. TremorTek is a tremor kinematic analytics investigational device which is used to measure maximum angular tremor amplitude at wrist of the injected limb (unit: degrees). Angular tremor amplitude is the measure of tremor severity. Reduction of angular tremor amplitude at wrist of the injected limb represents tremor improvement.</description>
          <population>The full analysis set (FAS) was defined as the subset of participants who received study medication (incobotulinumtoxinA or placebo) at least once, and for whom a post-baseline value of any efficacy variable was measured.</population>
          <units>degree</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.47" spread="0.63"/>
                    <measurement group_id="O2" value="0.07" spread="0.88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Least square (LS) means are from analysis of covariance (ANCOVA) with treatment and site included as fixed factors and baseline included as covariate.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.144</p_value>
            <method>ANCOVA</method>
            <param_type>LS mean difference</param_type>
            <param_value>-0.43</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.28</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.02</ci_lower_limit>
            <ci_upper_limit>0.16</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 4 in Maximum Log-transformed Accelerometric Tremor Amplitude at Wrist Level (Injected Limb)</title>
        <description>TremorTek is a tremor kinematic analytics investigational device which is used to measure maximum log-transformed accelerometric tremor amplitude at wrist level of the injected limb (unit: meter per square second [m/s˄2]). Log-transformed accelerometric tremor amplitude is a measure of tremor severity reflecting the non-vectoral intensity of tremor. Reduction of log-transformed accelerometric tremor amplitude at wrist level of the injected limb represents a tremor improvement.</description>
        <time_frame>Baseline up to Week 4</time_frame>
        <population>The FAS was defined as the subset of participants who received study medication (incobotulinumtoxinA or placebo) at least once, and for whom a post-baseline value of any efficacy variable was measured.</population>
        <group_list>
          <group group_id="O1">
            <title>IncobotulinumtoxinA 30 to 200 U</title>
            <description>Participants received incobotulinumtoxinA (also known as NT 201) between 30 to 200 U, powder for solution for injection, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo solution matched to the volume of incobotulinumtoxinA solution, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA placebo.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 4 in Maximum Log-transformed Accelerometric Tremor Amplitude at Wrist Level (Injected Limb)</title>
          <description>TremorTek is a tremor kinematic analytics investigational device which is used to measure maximum log-transformed accelerometric tremor amplitude at wrist level of the injected limb (unit: meter per square second [m/s˄2]). Log-transformed accelerometric tremor amplitude is a measure of tremor severity reflecting the non-vectoral intensity of tremor. Reduction of log-transformed accelerometric tremor amplitude at wrist level of the injected limb represents a tremor improvement.</description>
          <population>The FAS was defined as the subset of participants who received study medication (incobotulinumtoxinA or placebo) at least once, and for whom a post-baseline value of any efficacy variable was measured.</population>
          <units>log[m/s˄2]</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.73" spread="0.63"/>
                    <measurement group_id="O2" value="0.05" spread="0.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 4 in Fahn-Tolosa-Marin (FTM) Tremor Score in Injected Limb (Item 5 [Right Upper Extremity] or 6 [Left Upper Extremity])</title>
        <description>The FTM tremor rating scale is used for evaluation of tremor severity and function and consists of three parts (A, B, C). For this outcome measure the score of FTM scale item 5 (&quot;right upper extremity&quot;) or item 6 (&quot;left upper extremity&quot;) is used (both items are from part A). The outcome values are calculated as the sum of the three functions &quot;at rest&quot;, &quot;with posture holding&quot;, and &quot;with action and intention&quot;. The score for each item ranges from 0 (normal) to 4 (severe), that is, the possible values range from 0 to 12.</description>
        <time_frame>Baseline up to Week 4</time_frame>
        <population>The FAS was defined as the subset of participants who received study medication (incobotulinumtoxinA or placebo) at least once, and for whom a post-baseline value of any efficacy variable was measured.</population>
        <group_list>
          <group group_id="O1">
            <title>IncobotulinumtoxinA 30 to 200 U</title>
            <description>Participants received incobotulinumtoxinA (also known as NT 201) between 30 to 200 U, powder for solution for injection, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo solution matched to the volume of incobotulinumtoxinA solution, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA placebo.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 4 in Fahn-Tolosa-Marin (FTM) Tremor Score in Injected Limb (Item 5 [Right Upper Extremity] or 6 [Left Upper Extremity])</title>
          <description>The FTM tremor rating scale is used for evaluation of tremor severity and function and consists of three parts (A, B, C). For this outcome measure the score of FTM scale item 5 (&quot;right upper extremity&quot;) or item 6 (&quot;left upper extremity&quot;) is used (both items are from part A). The outcome values are calculated as the sum of the three functions &quot;at rest&quot;, &quot;with posture holding&quot;, and &quot;with action and intention&quot;. The score for each item ranges from 0 (normal) to 4 (severe), that is, the possible values range from 0 to 12.</description>
          <population>The FAS was defined as the subset of participants who received study medication (incobotulinumtoxinA or placebo) at least once, and for whom a post-baseline value of any efficacy variable was measured.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.9" spread="1.9"/>
                    <measurement group_id="O2" value="-0.5" spread="1.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 4 in FTM Motor Performance Score (Items 11-15)</title>
        <description>The FTM tremor rating scale was used for evaluation of tremor severity and function. This investigator-assessed scale consists of 3 parts (A, B and C). Part A: Tremor location/Severity rating (items 1-10); Part B: Specific motor tasks / Function rating (items 11-15). Ratings for five motor tasks (handwriting, drawing [large/small spiral, line], and pouring); and Part C: Functional disabilities resulting from tremor/activities of daily living (items 16-23). For this outcome measure, the sum of the five FTM motor performance items (from Part B) were used: item 11 ('handwriting for dominant hand only' - irrespective of its injection or non-injection), items 12 to 15 ('drawing large and small spiral', 'line drawing', 'pouring' for the injected upper limb). The score for each item ranges from 0 (normal) to 4 (severe). Possible values range for total FTM motor performance score: 0-20.</description>
        <time_frame>Baseline up to Week 4</time_frame>
        <population>The FAS was defined as the subset of participants who received study medication (incobotulinumtoxinA or placebo) at least once, and for whom a post-baseline value of any efficacy variable was measured.</population>
        <group_list>
          <group group_id="O1">
            <title>IncobotulinumtoxinA 30 to 200 U</title>
            <description>Participants received incobotulinumtoxinA (also known as NT 201) between 30 to 200 U, powder for solution for injection, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo solution matched to the volume of incobotulinumtoxinA solution, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA placebo.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 4 in FTM Motor Performance Score (Items 11-15)</title>
          <description>The FTM tremor rating scale was used for evaluation of tremor severity and function. This investigator-assessed scale consists of 3 parts (A, B and C). Part A: Tremor location/Severity rating (items 1-10); Part B: Specific motor tasks / Function rating (items 11-15). Ratings for five motor tasks (handwriting, drawing [large/small spiral, line], and pouring); and Part C: Functional disabilities resulting from tremor/activities of daily living (items 16-23). For this outcome measure, the sum of the five FTM motor performance items (from Part B) were used: item 11 ('handwriting for dominant hand only' - irrespective of its injection or non-injection), items 12 to 15 ('drawing large and small spiral', 'line drawing', 'pouring' for the injected upper limb). The score for each item ranges from 0 (normal) to 4 (severe). Possible values range for total FTM motor performance score: 0-20.</description>
          <population>The FAS was defined as the subset of participants who received study medication (incobotulinumtoxinA or placebo) at least once, and for whom a post-baseline value of any efficacy variable was measured.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.8" spread="1.6"/>
                    <measurement group_id="O2" value="-0.8" spread="2.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Participant's Global Impression of Change Scale (GICS) at Week 4</title>
        <description>The GICS was used to measure the participant's impression of change due to treatment. The response option was a common 7-point Likert scale, with the following values: +3 (very much improved); +2 (much improved); +1 (minimally improved); 0 (no change); -1 (minimally worse); -2 (much worse); -3 (very much worse).</description>
        <time_frame>Week 4</time_frame>
        <population>The FAS was defined as the subset of participants who received study medication (incobotulinumtoxinA or placebo) at least once, and for whom a post-baseline value of any efficacy variable was measured.</population>
        <group_list>
          <group group_id="O1">
            <title>IncobotulinumtoxinA 30 to 200 U</title>
            <description>Participants received incobotulinumtoxinA (also known as NT 201) between 30 to 200 U, powder for solution for injection, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo solution matched to the volume of incobotulinumtoxinA solution, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA placebo.</description>
          </group>
        </group_list>
        <measure>
          <title>Participant's Global Impression of Change Scale (GICS) at Week 4</title>
          <description>The GICS was used to measure the participant's impression of change due to treatment. The response option was a common 7-point Likert scale, with the following values: +3 (very much improved); +2 (much improved); +1 (minimally improved); 0 (no change); -1 (minimally worse); -2 (much worse); -3 (very much worse).</description>
          <population>The FAS was defined as the subset of participants who received study medication (incobotulinumtoxinA or placebo) at least once, and for whom a post-baseline value of any efficacy variable was measured.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6" spread="0.6"/>
                    <measurement group_id="O2" value="0.3" spread="0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Investigator's Global Impression of Change Scale (GICS) at Week 4</title>
        <description>The GICS was used to measure the investigator's impression of change due to treatment. The response option was a common 7-point Likert scale, with the following values: +3 (very much improved); +2 (much improved); +1 (minimally improved); 0 (no change); -1 (minimally worse); -2 (much worse); -3 (very much worse).</description>
        <time_frame>Week 4</time_frame>
        <population>The FAS was defined as the subset of participants who received study medication (incobotulinumtoxinA or placebo) at least once, and for whom a post-baseline value of any efficacy variable was measured.</population>
        <group_list>
          <group group_id="O1">
            <title>IncobotulinumtoxinA 30 to 200 U</title>
            <description>Participants received incobotulinumtoxinA (also known as NT 201) between 30 to 200 U, powder for solution for injection, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo solution matched to the volume of incobotulinumtoxinA solution, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA placebo.</description>
          </group>
        </group_list>
        <measure>
          <title>Investigator's Global Impression of Change Scale (GICS) at Week 4</title>
          <description>The GICS was used to measure the investigator's impression of change due to treatment. The response option was a common 7-point Likert scale, with the following values: +3 (very much improved); +2 (much improved); +1 (minimally improved); 0 (no change); -1 (minimally worse); -2 (much worse); -3 (very much worse).</description>
          <population>The FAS was defined as the subset of participants who received study medication (incobotulinumtoxinA or placebo) at least once, and for whom a post-baseline value of any efficacy variable was measured.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8" spread="0.7"/>
                    <measurement group_id="O2" value="0.1" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From screening up to Week 24</time_frame>
      <desc>The investigator asked the participant for adverse events (AEs) systematically at each visit.</desc>
      <group_list>
        <group group_id="E1">
          <title>IncobotulinumtoxinA 30 to 200 U</title>
          <description>Participants received incobotulinumtoxinA (also known as NT 201) between 30 to 200 U, powder for solution for injection, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Participants received placebo solution matched to the volume of incobotulinumtoxinA solution, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA placebo.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (19.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chest discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (19.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Glaucoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Injection site bruising</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Injection site pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Eyelid infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Genital infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Nail infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Tooth infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Ankle fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Head injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Joint injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood cholesterol increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetes mellitus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Exostosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Breast mass</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Publication of study information usually requires agreement with the sponsor. In case of justified doubts by the sponsor, the INVESTIGATOR will consider these doubts in the publication as long as the scientific neutrality is not affected.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Public Disclosure Manager</name_or_title>
      <organization>Merz Pharmaceuticals GmbH</organization>
      <phone>+49 69 1503 1</phone>
      <email>clinicaltrials@merz.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/NCT02207946
org study id: MRZ60201_2094_1
nct id: NCT02207946
lead sponsor: 
has dmc: No
The objective of this study is to assess the efficacy and safety of a single,
      kinematic-analysis-based intramuscular injection of NT 201, compared with placebo, in
      moderate to marked essential tremor of the upper limb.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change From Baseline to Week 4 in Maximum Angular Tremor Amplitude of the Wrist (Injected Limb)
time frame: Baseline up to Week 4
description: No primary efficacy variables are defined for this study. One of the secondary outcome measures is used for CTgov protocol registration and results reporting purposes only. TremorTek is a tremor kinematic analytics investigational device which is used to measure maximum angular tremor amplitude at wrist of the injected limb (unit: degrees). Angular tremor amplitude is the measure of tremor severity. Reduction of angular tremor amplitude at wrist of the injected limb represents tremor improvement.
measure: Change From Baseline to Week 4 in Maximum Log-transformed Accelerometric Tremor Amplitude at Wrist Level (Injected Limb)
time frame: Baseline up to Week 4
description: TremorTek is a tremor kinematic analytics investigational device which is used to measure maximum log-transformed accelerometric tremor amplitude at wrist level of the injected limb (unit: meter per square second [m/s˄2]). Log-transformed accelerometric tremor amplitude is a measure of tremor severity reflecting the non-vectoral intensity of tremor. Reduction of log-transformed accelerometric tremor amplitude at wrist level of the injected limb represents a tremor improvement.
measure: Change From Baseline to Week 4 in Fahn-Tolosa-Marin (FTM) Tremor Score in Injected Limb (Item 5 [Right Upper Extremity] or 6 [Left Upper Extremity])
time frame: Baseline up to Week 4
description: The FTM tremor rating scale is used for evaluation of tremor severity and function and consists of three parts (A, B, C). For this outcome measure the score of FTM scale item 5 ("right upper extremity") or item 6 ("left upper extremity") is used (both items are from part A). The outcome values are calculated as the sum of the three functions "at rest", "with posture holding", and "with action and intention". The score for each item ranges from 0 (normal) to 4 (severe), that is, the possible values range from 0 to 12.
measure: Change From Baseline to Week 4 in FTM Motor Performance Score (Items 11-15)
time frame: Baseline up to Week 4
description: The FTM tremor rating scale was used for evaluation of tremor severity and function. This investigator-assessed scale consists of 3 parts (A, B and C). Part A: Tremor location/Severity rating (items 1-10); Part B: Specific motor tasks / Function rating (items 11-15). Ratings for five motor tasks (handwriting, drawing [large/small spiral, line], and pouring); and Part C: Functional disabilities resulting from tremor/activities of daily living (items 16-23). For this outcome measure, the sum of the five FTM motor performance items (from Part B) were used: item 11 ('handwriting for dominant hand only' - irrespective of its injection or non-injection), items 12 to 15 ('drawing large and small spiral', 'line drawing', 'pouring' for the injected upper limb). The score for each item ranges from 0 (normal) to 4 (severe). Possible values range for total FTM motor performance score: 0-20.
measure: Participant's Global Impression of Change Scale (GICS) at Week 4
time frame: Week 4
description: The GICS was used to measure the participant's impression of change due to treatment. The response option was a common 7-point Likert scale, with the following values: +3 (very much improved); +2 (much improved); +1 (minimally improved); 0 (no change); -1 (minimally worse); -2 (much worse); -3 (very much worse).
measure: Investigator's Global Impression of Change Scale (GICS) at Week 4
time frame: Week 4
description: The GICS was used to measure the investigator's impression of change due to treatment. The response option was a common 7-point Likert scale, with the following values: +3 (very much improved); +2 (much improved); +1 (minimally improved); 0 (no change); -1 (minimally worse); -2 (much worse); -3 (very much worse).
arm group label: 200 Units incobotulinumtoxinA (Xeomin)
arm group type: Experimental
description: Single injection cycle, total dose of up to 200 Units, intramuscular injection into muscles of wrist (mandatory) and shoulder and/or elbow (both optional).
arm group label: Placebo
arm group type: Placebo Comparator
description: Single injection cycle, intramuscular injection into muscles of wrist (mandatory) and shoulder and/or elbow (both optional).
intervention type: Drug
intervention name: IncobotulinumtoxinA
description: Active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).
arm group label: 200 Units incobotulinumtoxinA (Xeomin)
other name: Xeomin
other name: NT 201
other name: Botulinum toxin type A (150 kiloDalton), free from complexing proteins
intervention type: Drug
intervention name: Placebo
description: Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Merz Medical Expert
role: Study Director
affiliation: Merz Pharmaceuticals GmbH
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: United States
citation: Jog M, Lee J, Scheschonka A, Chen R, Ismail F, Boulias C, Hobson D, King D, Althaus M, Simon O, Dersch H, Frucht S, Simpson DM. Tolerability and Efficacy of Customized IncobotulinumtoxinA Injections for Essential Tremor: A Randomized, Double-Blind, Placebo-Controlled Study. Toxins (Basel). 2020 Dec 20;12(12):807. doi: 10.3390/toxins12120807.
PMID: 33419261
responsible party type: Sponsor
mesh term: Tremor
mesh term: Essential Tremor
mesh term: Botulinum Toxins
mesh term: Botulinum Toxins, Type A
mesh term: abobotulinumtoxinA
mesh term: incobotulinumtoxinA
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 