<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/NCT01682148</url>
  </required_header>
  <id_info>
    <org_study_id>A-99-52120-162</org_study_id>
    <secondary_id>2011-005375-16</secondary_id>
    <nct_id>NCT01682148</nct_id>
  </id_info>
  <brief_title>Comparing Lower-concentration Dysport Treatment Targeted to the Neuromuscular Junction With Current Clinical Practice</brief_title>
  <acronym>NMJ</acronym>
  <official_title>A Phase III Prospective, Multi-center, Randomised, Evaluator-blinded Study to Compare Neuromuscular Junction (NMJ) Targeted Technique for Dysport Injections in Upper Limb Spasticity Post Stroke or Traumatic Brain Injury to the Technique Used in Current Clinical Practice</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ipsen</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ipsen</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of the study was to compare Dysport treatment results (as assessed by Modified&#xD;
      Ashworth Scale (MAS) in the elbow joint 4 weeks post treatment) following two treatment&#xD;
      techniques: the current clinical practice injection technique using high-concentration&#xD;
      dilution (300 U/mL Dysport) versus the neuromuscular junction (NMJ)-targeted injection&#xD;
      technique using low-concentration dilution (100 U/mL Dysport). The hypothesis was that one&#xD;
      high-volume, low-concentration injection located centrally in the area/band of the NMJ zones&#xD;
      would be as effective as the technique used in current medical practice.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This was a randomised, evaluator-blinded, comparative, parallel group, multicentre study,&#xD;
      conducted in four countries (Denmark, Finland, Norway and Sweden). For each subject, the&#xD;
      primary efficacy assessments using MAS were performed by the same blinded evaluator, and&#xD;
      every effort was made at each site to ensure that the MAS evaluator was the same person&#xD;
      throughout the study. Dysport doses were to follow clinical practice for subjects suffering&#xD;
      from upper limb spasticity position pattern type 1, 3 or 4 post stroke or traumatic brain&#xD;
      injury.&#xD;
&#xD;
      The hypothesis for this study was that one low-concentration botulinum neurotoxin type A&#xD;
      (BoNT-A) injection per muscle, centrally located in the area/band of the NMJ zones, would&#xD;
      spread to and block the surrounding NMJ zones and be as effective as the technique used today&#xD;
      in clinical practice. The possibility to reduce the number of injection points would decrease&#xD;
      the risk of injection discomfort, pain and injection site bleeding for the patient. A&#xD;
      simplified injection technique with one injection per muscle and in a defined location would&#xD;
      also benefit physicians.&#xD;
&#xD;
      At Baseline (Visit 1), subjects were randomised to one of two treatment groups:&#xD;
&#xD;
        -  Group 1: Current clinical practice technique and high-concentration dilution: Dysport&#xD;
           300 U/mL.&#xD;
&#xD;
        -  Group 2: NMJ targeted technique and low-concentration dilution: Dysport 100 U/mL.&#xD;
&#xD;
      Each subject visited the clinic on at least three occasions:&#xD;
&#xD;
        -  Baseline (Visit 1): Screening, randomisation and Dysport treatment.&#xD;
&#xD;
        -  Week 4 (Visit 2): Treatment follow-up, 4 weeks after Dysport treatment.&#xD;
&#xD;
        -  Week 12 (Visit 3): Treatment and study follow-up, 12 weeks after Dysport treatment.&#xD;
&#xD;
      For subjects not receiving any post study BoNT-A injection at Week 12 due to remaining&#xD;
      treatment effect, an extra visit (Visit 4) for study follow-up was to take place at the next&#xD;
      routine visit planned for a new BoNT-A injection, at the latest 24 weeks post study&#xD;
      injection.&#xD;
&#xD;
      The duration of each subject's study period was at a minimum 12 weeks and maximum 24 weeks.&#xD;
      The overall duration of the study was planned to be approximately 36 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The study was terminated early due to slow recruitment.&#xD;
  </why_stopped>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">March 2015</completion_date>
  <primary_completion_date type="Actual">March 2015</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline for Elbow Flexors Muscle Tone as Measured by the Modified Ashworth Scale (MAS) at Week 4</measure>
    <time_frame>Baseline to Week 4</time_frame>
    <description>A clinically relevant change was one level decrease on the MAS scale. Subjects meeting the defined decrease at Week 4 were considered as responders in the primary efficacy analysis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline for Elbow Flexors Muscle Tone as Measured by the Modified Ashworth Scale (MAS) at Week 4 and Week 12</measure>
    <time_frame>Baseline to Week 12</time_frame>
    <description>Increased muscle tone in elbow flexors was assessed using the MAS. Scale ranges from 0 (no increase in muscle tone) to 4 (affected part rigid in flexion or extension).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline for Elbow Flexors Muscle Tone as Measured by the MAS at Week 12</measure>
    <time_frame>Baseline to Week 12</time_frame>
    <description>A clinically relevant change was one level decrease on the MAS scale. Subjects meeting the defined decrease at Week 12 were considered as responders.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline of Spasticity Related Pain Measured by Visual Analogue Scale (VAS), Assessed by the Subject</measure>
    <time_frame>Baseline, Week 4 and Week 12</time_frame>
    <description>Pain assessment using the VAS. The VAS was a 10 cm straight horizontal line scoring scale. Score range on VAS was from 0 to 10 where 0 indicated no pain and 10 indicated worst pain imaginable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Injection Site Pain Measured by VAS at Day 1.</measure>
    <time_frame>Baseline</time_frame>
    <description>Pain assessment using the VAS. The VAS was a 100 mm straight horizontal line scoring scale. Score range on VAS was from 0 to 100 where 0 indicated no pain and 100 indicated worst pain imaginable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Achievement of the Primary Goal Measured by Goal Attainment Scale (GAS)</measure>
    <time_frame>Up to Week 12</time_frame>
    <description>At Baseline, an agreed primary goal related to elbow flexion in one of the following categories was determined: active function, impairment, involuntary movement, mobility, pain passive function or other. Each goal was usually rated -1, unless the subject was as bad as he/she could be in that particular goal area, in which case the Baseline score was -2. The evaluator rated the outcome score at Week 4 or Week 12, depending on the time point defined at the baseline visit (Visit 1), using the GAS five-point scale (-2, -1, 0, +1 and +2).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subject Global Evaluation of Treatment Effect</measure>
    <time_frame>Up to Week 24</time_frame>
    <description>Comparison of treatment effect between previous (prestudy) and study treatment cycles assessed by the subject at the end of study (Week 12 up to Week 24 (Visit 3 or Visit 4)). Categorised as follows: Much worse / Worse / Same / Better / Much better.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Investigator Preference of Injection Technique</measure>
    <time_frame>Following last visit of the last subject at each site</time_frame>
    <description>When all patients at the site had completed the study (last subject last visit) a global assessment of the injection technique was to be made by the Investigators. The following question was answered: &quot;Based on your experience during this study, which injection technique do you prefer?&quot;</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Arm Spasticity</condition>
  <arm_group>
    <arm_group_label>NMJ Targeted</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>NMJ targeted technique and low-concentration dilution (Dysport 100 U/mL). The same number and sites of injections/deposits per muscle were given as per prestudy. With a Dysport dilution of 300 U/mL the volume to be injected varied between 0.1 mL and 0.7 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Current Clinical Practice</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Current clinical practice technique and high-concentration dilution (Dysport 300 U/mL).&#xD;
A single injection per muscle was given in the midline of the band of NMJ zones. With a Dysport dilution of 100 U/mL the volume to be injected varied between 0.4 mL and 2.0 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Botulinum toxin type A</intervention_name>
    <arm_group_label>Current Clinical Practice</arm_group_label>
    <arm_group_label>NMJ Targeted</arm_group_label>
    <other_name>AbobotulinumtoxinA (Dysport®)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Provision of written informed consent prior to any study related procedures.&#xD;
&#xD;
          -  Subjects male or female, aged 18 years or older.&#xD;
&#xD;
          -  Upper limb spasticity post stroke or traumatic brain injury.&#xD;
&#xD;
          -  Spasticity position pattern type 1, 3 or 4.&#xD;
&#xD;
          -  Elbow flexor muscles spasticity MAS 2 to 3.&#xD;
&#xD;
          -  At least 2 consecutive previous treatment cycles of BoNT-A for current diagnosis.&#xD;
&#xD;
          -  The latest treatment cycle demonstrating good treatment efficacy where the Dysport&#xD;
             dose administered was considered to be adequate according to Investigator judgement.&#xD;
&#xD;
          -  Need of the same treatment modality in muscle (m.) brachialis, m. biceps brachii, m.&#xD;
             brachioradialis, m. flexor carpi ulnaris, m. flexor carpi radialis as the previous&#xD;
             treatment cycle.&#xD;
&#xD;
          -  Last BoNT-A treatment 12-24 weeks ago.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Poor response to BoNT-A treatment, according to Investigator.&#xD;
&#xD;
          -  Need of Dysport doses &gt;800 U in the upper limb.&#xD;
&#xD;
          -  Concomitant treatment with BoNT-A for other indications than spasticity.&#xD;
&#xD;
          -  Any elbow flexor contracture prohibiting MAS evaluation and/or elbow flexion&#xD;
             improvement of at least 1 step on the MAS.&#xD;
&#xD;
          -  Cutaneous or joint inflammation in the affected upper limb.&#xD;
&#xD;
          -  Was likely to start other spasticity treatment during the study.&#xD;
&#xD;
          -  Was likely to start physiotherapy treatment during the study.&#xD;
&#xD;
          -  Other ongoing neurological disorder (e.g., myasthenia gravis).&#xD;
&#xD;
          -  History of dysphagia or aspiration.&#xD;
&#xD;
          -  Use of agents interfering with neuromuscular transmission (e.g., aminoglycosides).&#xD;
&#xD;
          -  Treated with an investigational medicinal product within 30 days before start of the&#xD;
             study.&#xD;
&#xD;
          -  Known sensitivity to BoNT-A or any components of Dysport.&#xD;
&#xD;
          -  Was at risk of pregnancy or was lactating. Females of childbearing potential must have&#xD;
             provided a negative pregnancy test (urinary human chorionic gonadotropin (U-hCG)) at&#xD;
             Visit 1 and must have been using adequate contraception. Non-childbearing potential&#xD;
             was defined as post-menopause for at least one year, surgical sterilisation or&#xD;
             hysterectomy at least three months before the start of the study.&#xD;
&#xD;
          -  Had a history of, or known current, problems with alcohol or drug abuse.&#xD;
&#xD;
          -  Had a mental condition rendering the subject unable to understand the nature, scope&#xD;
             and possible consequences of the study, and/or evidence of an uncooperative attitude.&#xD;
&#xD;
          -  Had abnormal Baseline findings, any other medical condition(s) or laboratory findings&#xD;
             that, in the opinion of the investigator, might have jeopardised the subject's safety&#xD;
             or decreased the chance of obtaining satisfactory data needed to achieve the&#xD;
             objective(s) of the study.&#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>Ipsen Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Ipsen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Aalborg Sygehus Nord</name>
      <address>
        <city>Aalborg</city>
        <zip>9000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Glostrup Hospital</name>
      <address>
        <city>Glostrup</city>
        <zip>2600</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regionshospitalet Hammel</name>
      <address>
        <city>Hammel</city>
        <zip>8450</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bispebjerg Hospital</name>
      <address>
        <city>København NV</city>
        <zip>2400</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Roskilde Hospital</name>
      <address>
        <city>Roskilde</city>
        <zip>4000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vejle Hospital</name>
      <address>
        <city>Vejle</city>
        <zip>7100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regionshopsitalet Viborg</name>
      <address>
        <city>Viborg</city>
        <zip>8800</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Karelia Central Hospital</name>
      <address>
        <city>Joensuu</city>
        <zip>80210</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Hospital of Central Finland</name>
      <address>
        <city>Jyväskylä</city>
        <zip>40503</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Haukeland University Hospital</name>
      <address>
        <city>Bergen</city>
        <zip>5021</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sykehuset Telemark HF</name>
      <address>
        <city>Skien</city>
        <zip>, 3700</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mälarsjukhuset MSE</name>
      <address>
        <city>Eskilstuna</city>
        <zip>631-88</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sahlgrenska University Hospital</name>
      <address>
        <city>Göteborg</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hallands Sjukhus, Neurology Clinic</name>
      <address>
        <city>Halmstad</city>
        <zip>30185</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sundsvall-Härnösand, Rehabilitation Medicine</name>
      <address>
        <city>Härnösand</city>
        <zip>87182</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nyköpings Lasarett,</name>
      <address>
        <city>Nyköping</city>
        <zip>61185</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neurology Clinic Stockholm</name>
      <address>
        <city>Stockholm</city>
        <zip>114 33</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Danderyds Hospital,</name>
      <address>
        <city>Stockholm</city>
        <zip>18288</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neurorehab Sävar</name>
      <address>
        <city>Sävar</city>
        <zip>91831</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rehabilitation Center Gotland</name>
      <address>
        <city>Visby</city>
        <zip>62184</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ystad Lasarett</name>
      <address>
        <city>Ystad</city>
        <zip>27133</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Örnsköldsviks Sjukhus, Neurology Clinic</name>
      <address>
        <city>Örnsköldsvik</city>
        <zip>891 89</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Östersunds Rehabilitation Center</name>
      <address>
        <city>Östersund</city>
        <zip>83102</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
    <country>Finland</country>
    <country>Norway</country>
    <country>Sweden</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>September 6, 2012</study_first_submitted>
  <study_first_submitted_qc>September 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2012</study_first_posted>
  <results_first_submitted>December 28, 2016</results_first_submitted>
  <results_first_submitted_qc>October 4, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">February 18, 2019</results_first_posted>
  <last_update_submitted>September 15, 2022</last_update_submitted>
  <last_update_submitted_qc>September 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 27, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Dysport</keyword>
  <keyword>arm spasticity</keyword>
  <keyword>Modified Ashworth Scale</keyword>
  <keyword>neuromuscular junction</keyword>
  <keyword>Botulinum toxin</keyword>
  <keyword>upper limb spasticity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Muscle Spasticity</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>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized, and study documents will be redacted to protect the privacy of study participants.&#xD;
Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.</ipd_description>
    <ipd_time_frame>Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.</ipd_time_frame>
    <ipd_access_criteria>Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).</ipd_access_criteria>
    <ipd_url>https://vivli.org/members/ourmembers/</ipd_url>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>From September 2012, subjects were recruited across 20 sites in four countries: Denmark (5 sites), Finland (2 sites), Norway (2 sites) and Sweden (11 sites). Due to slow recruitment, the study was terminated early.</recruitment_details>
      <pre_assignment_details>272 subjects were planned to be randomised (136 subjects in each group). In total, 100 subjects were enrolled and 88 (44 subjects in each group) were randomised and received study medication; 12 subjects were screening failures.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>NMJ Targeted</title>
          <description>Neuromuscular junction (NMJ) targeted technique and low-concentration dilution (Dysport 100 U/mL): A single injection per muscle was given in the midline of the band of NMJ zones. With a Dysport dilution of 100 U/mL the volume to be injected varied between 0.4 mL and 2.0 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment.</description>
        </group>
        <group group_id="P2">
          <title>Current Clinical Practice</title>
          <description>Current clinical practice technique and high-concentration dilution (Dysport 300 U/mL): The same number and sites of injections/deposits per muscle were given as per prestudy. With a Dysport dilution of 300 U/mL the volume to be injected varied between 0.1 mL and 0.7 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="44"/>
                <participants group_id="P2" count="44"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="40"/>
                <participants group_id="P2" count="41"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The intention-to-treat (ITT) population was defined as all treated subjects having at least one Baseline assessment of the primary efficacy parameter. The ITT population was analysed using subjects as randomised.</population>
      <group_list>
        <group group_id="B1">
          <title>NMJ Targeted</title>
          <description>NMJ targeted technique and low-concentration dilution (Dysport 100 U/mL): A single injection per muscle was given in the midline of the band of NMJ zones. With a Dysport dilution of 100 U/mL the volume to be injected varied between 0.4 mL and 2.0 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment.</description>
        </group>
        <group group_id="B2">
          <title>Current Clinical Practice</title>
          <description>Current clinical practice technique and high-concentration dilution (Dysport 300 U/mL): The same number and sites of injections/deposits per muscle were given as per prestudy. With a Dysport dilution of 300 U/mL the volume to be injected varied between 0.1 mL and 0.7 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment.</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="44"/>
            <count group_id="B2" value="44"/>
            <count group_id="B3" value="88"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="57.1" spread="11.4"/>
                    <measurement group_id="B2" value="60.3" spread="14.4"/>
                    <measurement group_id="B3" value="58.7" spread="13.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Sweden</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Norway</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Finland</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Denmark</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline for Elbow Flexors Muscle Tone as Measured by the Modified Ashworth Scale (MAS) at Week 4</title>
        <description>A clinically relevant change was one level decrease on the MAS scale. Subjects meeting the defined decrease at Week 4 were considered as responders in the primary efficacy analysis.</description>
        <time_frame>Baseline to Week 4</time_frame>
        <population>The primary analysis was based on both the ITT and Per Protocol (PP) populations. The ITT population was all treated subjects having at least one Baseline assessment of the primary efficacy parameter. The PP population was all subjects in the ITT population for whom no major protocol violations or deviations occurred until Week 4 (Visit 2).</population>
        <group_list>
          <group group_id="O1">
            <title>NMJ Targeted (ITT Population)</title>
            <description>NMJ targeted technique and low-concentration dilution (Dysport 100 U/mL): A single injection per muscle was given in the midline of the band of NMJ zones. With a Dysport dilution of 100 U/mL the volume to be injected varied between 0.4 mL and 2.0 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment.</description>
          </group>
          <group group_id="O2">
            <title>Current Clinical Practice (ITT Population)</title>
            <description>Current clinical practice technique and high-concentration dilution (Dysport 300 U/mL): The same number and sites of injections/deposits per muscle were given as per prestudy. With a Dysport dilution of 300 U/mL the volume to be injected varied between 0.1 mL and 0.7 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment.</description>
          </group>
          <group group_id="O3">
            <title>NMJ Targeted (PP Population)</title>
            <description>NMJ targeted technique and low-concentration dilution (Dysport 100 U/mL): A single injection per muscle was given in the midline of the band of NMJ zones. With a Dysport dilution of 100 U/mL the volume to be injected varied between 0.4 mL and 2.0 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment.</description>
          </group>
          <group group_id="O4">
            <title>Current Clinical Practice (PP Population)</title>
            <description>Current clinical practice technique and high-concentration dilution (Dysport 300 U/mL): The same number and sites of injections/deposits per muscle were given as per prestudy. With a Dysport dilution of 300 U/mL the volume to be injected varied between 0.1 mL and 0.7 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline for Elbow Flexors Muscle Tone as Measured by the Modified Ashworth Scale (MAS) at Week 4</title>
          <description>A clinically relevant change was one level decrease on the MAS scale. Subjects meeting the defined decrease at Week 4 were considered as responders in the primary efficacy analysis.</description>
          <population>The primary analysis was based on both the ITT and Per Protocol (PP) populations. The ITT population was all treated subjects having at least one Baseline assessment of the primary efficacy parameter. The PP population was all subjects in the ITT population for whom no major protocol violations or deviations occurred until Week 4 (Visit 2).</population>
          <units>responders</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="25"/>
                <count group_id="O4" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                    <measurement group_id="O2" value="32"/>
                    <measurement group_id="O3" value="17"/>
                    <measurement group_id="O4" value="20"/>
                  </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>A responder was defined as a subject with at least one level decrease on the MAS scale.</groups_desc>
            <non_inferiority_type>Non-Inferiority or Equivalence (legacy)</non_inferiority_type>
            <non_inferiority_desc>Based on a responder rate (π) of 63% in the reference group, a clinically relevant delta (Δ) of 17%, α=2.5% (one sided) and power=80%, the sample size estimate yielded 122 valid subjects per group. Including a 10% addition for premature withdrawals, 136 subjects per group were necessary to be randomised in the study (i.e., a total of 272 subjects).</non_inferiority_desc>
            <p_value>0.0986</p_value>
            <p_value_desc>Based on a generalised linear model including factors for treatment.</p_value_desc>
            <method>Generalised linear model</method>
            <param_type>Treatment difference</param_type>
            <param_value>-0.1673</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.3630</ci_lower_limit>
            <ci_upper_limit>0.0284</ci_upper_limit>
            <estimate_desc>Difference of the two clinical success rates (NMJ Targeted minus Current Clinical Practice).</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A responder was defined as a subject with at least one level decrease on the MAS scale.</groups_desc>
            <non_inferiority_type>Non-Inferiority or Equivalence (legacy)</non_inferiority_type>
            <non_inferiority_desc>Based on a π of 63% in the reference group, a clinically relevant Δ of 17%, α=2.5% (one sided) and power=80%, the sample size estimate yielded 122 valid subjects per group. Including a 10% addition for premature withdrawals, 136 subjects per group were necessary to be randomised in the study (i.e., a total of 272 subjects).</non_inferiority_desc>
            <p_value>0.5682</p_value>
            <p_value_desc>Based on a generalised linear model including factors for spasticity pattern.</p_value_desc>
            <method>Generalised linear model</method>
            <param_type>Treatment difference</param_type>
            <param_value>-0.1673</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.3630</ci_lower_limit>
            <ci_upper_limit>0.0284</ci_upper_limit>
            <estimate_desc>Difference of the two clinical success rates (NMJ Targeted minus Current Clinical Practice).</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A responder was defined as a subject with at least one level decrease on the MAS scale.</groups_desc>
            <non_inferiority_type>Non-Inferiority or Equivalence (legacy)</non_inferiority_type>
            <non_inferiority_desc>Based on a π of 63% in the reference group, a clinically relevant Δ of 17%, α=2.5% (one sided) and power=80%, the sample size estimate yielded 122 valid subjects per group. Including a 10% addition for premature withdrawals, 136 subjects per group were necessary to be randomised in the study (i.e., a total of 272 subjects).</non_inferiority_desc>
            <p_value>0.8543</p_value>
            <p_value_desc>Based on a generalised linear model including factors for country.</p_value_desc>
            <method>Generalised linear model</method>
            <param_type>Treatment difference</param_type>
            <param_value>-0.1673</param_value>
            <ci_percent>5</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.3630</ci_lower_limit>
            <ci_upper_limit>0.0284</ci_upper_limit>
            <estimate_desc>Difference of the two clinical success rates (NMJ Targeted minus Current Clinical Practice).</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A responder was defined as a subject with at least one level decrease on the MAS scale.</groups_desc>
            <non_inferiority_type>Non-Inferiority or Equivalence (legacy)</non_inferiority_type>
            <non_inferiority_desc>Based on a π of 63% in the reference group, a clinically relevant Δ of 17%, α=2.5% (one sided) and power=80%, the sample size estimate yielded 122 valid subjects per group. Including a 10% addition for premature withdrawals, 136 subjects per group were necessary to be randomised in the study (i.e., a total of 272 subjects).</non_inferiority_desc>
            <p_value>0.9167</p_value>
            <p_value_desc>Based on a generalised linear model including factors for MAS at Baseline.</p_value_desc>
            <method>Generalised linear model</method>
            <param_type>Treatment difference</param_type>
            <param_value>-0.1673</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.3630</ci_lower_limit>
            <ci_upper_limit>0.0284</ci_upper_limit>
            <estimate_desc>Difference of the two clinical success rates (NMJ Targeted minus Current Clinical Practice).</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A responder was defined as a subject with at least one level decrease on the MAS scale.</groups_desc>
            <non_inferiority_type>Non-Inferiority or Equivalence (legacy)</non_inferiority_type>
            <non_inferiority_desc>Based on a π of 63% in the reference group, a clinically relevant Δ of 17%, α=2.5% (one sided) and power=80%, the sample size estimate yielded 122 valid subjects per group. Including a 10% addition for premature withdrawals, 136 subjects per group were necessary to be randomised in the study (i.e., a total of 272 subjects).</non_inferiority_desc>
            <p_value>0.6052</p_value>
            <p_value_desc>Based on a generalised linear model including factors for treatment.</p_value_desc>
            <method>Generalised linear model</method>
            <param_type>Treatment difference</param_type>
            <param_value>0.0707</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.1948</ci_lower_limit>
            <ci_upper_limit>0.3362</ci_upper_limit>
            <estimate_desc>Difference of the two clinical success rates (NMJ Targeted minus Current Clinical Practice).</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A responder was defined as a subject with at least one level decrease on the MAS scale.</groups_desc>
            <non_inferiority_type>Non-Inferiority or Equivalence (legacy)</non_inferiority_type>
            <non_inferiority_desc>Based on a π of 63% in the reference group, a clinically relevant Δ of 17%, α=2.5% (one sided) and power=80%, the sample size estimate yielded 122 valid subjects per group. Including a 10% addition for premature withdrawals, 136 subjects per group were necessary to be randomised in the study (i.e., a total of 272 subjects).</non_inferiority_desc>
            <p_value>0.5369</p_value>
            <p_value_desc>Based on a generalised linear model including factors for spasticity pattern.</p_value_desc>
            <method>Generalised linear model</method>
            <param_type>Treatment difference</param_type>
            <param_value>0.0707</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.1948</ci_lower_limit>
            <ci_upper_limit>0.3362</ci_upper_limit>
            <estimate_desc>Difference of the two clinical success rates (NMJ Targeted minus Current Clinical Practice).</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A responder was defined as a subject with at least one level decrease on the MAS scale.</groups_desc>
            <non_inferiority_type>Non-Inferiority or Equivalence (legacy)</non_inferiority_type>
            <non_inferiority_desc>Based on a π of 63% in the reference group, a clinically relevant Δ of 17%, α=2.5% (one sided) and power=80%, the sample size estimate yielded 122 valid subjects per group. Including a 10% addition for premature withdrawals, 136 subjects per group were necessary to be randomised in the study (i.e., a total of 272 subjects).</non_inferiority_desc>
            <p_value>0.7732</p_value>
            <p_value_desc>Based on a generalised linear model including factors for country.</p_value_desc>
            <method>Generalised linear model</method>
            <param_type>Treatment difference</param_type>
            <param_value>0.0707</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.1948</ci_lower_limit>
            <ci_upper_limit>0.3362</ci_upper_limit>
            <estimate_desc>Difference of the two clinical success rates (NMJ Targeted minus Current Clinical Practice).</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A responder was defined as a subject with at least one level decrease on the MAS scale.</groups_desc>
            <non_inferiority_type>Non-Inferiority or Equivalence (legacy)</non_inferiority_type>
            <non_inferiority_desc>Based on a π of 63% in the reference group, a clinically relevant Δ of 17%, α=2.5% (one sided) and power=80%, the sample size estimate yielded 122 valid subjects per group. Including a 10% addition for premature withdrawals, 136 subjects per group were necessary to be randomised in the study (i.e., a total of 272 subjects).</non_inferiority_desc>
            <p_value>0.1758</p_value>
            <p_value_desc>Based on a generalised linear model including factors for MAS at Baseline.</p_value_desc>
            <method>Generalised linear model</method>
            <param_type>Treatment difference</param_type>
            <param_value>0.0707</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.1948</ci_lower_limit>
            <ci_upper_limit>0.3362</ci_upper_limit>
            <estimate_desc>Difference of the two clinical success rates (NMJ Targeted minus Current Clinical Practice).</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline for Elbow Flexors Muscle Tone as Measured by the Modified Ashworth Scale (MAS) at Week 4 and Week 12</title>
        <description>Increased muscle tone in elbow flexors was assessed using the MAS. Scale ranges from 0 (no increase in muscle tone) to 4 (affected part rigid in flexion or extension).</description>
        <time_frame>Baseline to Week 12</time_frame>
        <population>ITT population: all treated subjects having at least one Baseline assessment of the primary efficacy parameter. Only subjects with non-missing values were included in this analysis.&#xD;
CCP=Current Clinical Practice; N'=number of subjects with data at each time point for each treatment group; NMJ=neuromuscular junction.</population>
        <group_list>
          <group group_id="O1">
            <title>NMJ Targeted</title>
            <description>NMJ targeted technique and low-concentration dilution (Dysport 100 U/mL): A single injection per muscle was given in the midline of the band of NMJ zones. With a Dysport dilution of 100 U/mL the volume to be injected varied between 0.4 mL and 2.0 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment.</description>
          </group>
          <group group_id="O2">
            <title>Current Clinical Practice</title>
            <description>Current clinical practice technique and high-concentration dilution (Dysport 300 U/mL): The same number and sites of injections/deposits per muscle were given as per prestudy. With a Dysport dilution of 300 U/mL the volume to be injected varied between 0.1 mL and 0.7 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline for Elbow Flexors Muscle Tone as Measured by the Modified Ashworth Scale (MAS) at Week 4 and Week 12</title>
          <description>Increased muscle tone in elbow flexors was assessed using the MAS. Scale ranges from 0 (no increase in muscle tone) to 4 (affected part rigid in flexion or extension).</description>
          <population>ITT population: all treated subjects having at least one Baseline assessment of the primary efficacy parameter. Only subjects with non-missing values were included in this analysis.&#xD;
CCP=Current Clinical Practice; N'=number of subjects with data at each time point for each treatment group; NMJ=neuromuscular junction.</population>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="40"/>
                    <count group_id="O2" value="43"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5" lower_limit="-2" upper_limit="1"/>
                    <measurement group_id="O2" value="-1.0" lower_limit="-3" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="39"/>
                    <count group_id="O2" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="-2" upper_limit="1"/>
                    <measurement group_id="O2" value="0.0" lower_limit="-2" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline for Elbow Flexors Muscle Tone as Measured by the MAS at Week 12</title>
        <description>A clinically relevant change was one level decrease on the MAS scale. Subjects meeting the defined decrease at Week 12 were considered as responders.</description>
        <time_frame>Baseline to Week 12</time_frame>
        <population>ITT population: all treated subjects having at least one Baseline assessment of the primary efficacy parameter. Only subjects with non-missing values were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>NMJ Targeted</title>
            <description>NMJ targeted technique and low-concentration dilution (Dysport 100 U/mL): A single injection per muscle was given in the midline of the band of NMJ zones. With a Dysport dilution of 100 U/mL the volume to be injected varied between 0.4 mL and 2.0 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment.</description>
          </group>
          <group group_id="O2">
            <title>Current Clinical Practice</title>
            <description>Current clinical practice technique and high-concentration dilution (Dysport 300 U/mL): The same number and sites of injections/deposits per muscle were given as per prestudy. With a Dysport dilution of 300 U/mL the volume to be injected varied between 0.1 mL and 0.7 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline for Elbow Flexors Muscle Tone as Measured by the MAS at Week 12</title>
          <description>A clinically relevant change was one level decrease on the MAS scale. Subjects meeting the defined decrease at Week 12 were considered as responders.</description>
          <population>ITT population: all treated subjects having at least one Baseline assessment of the primary efficacy parameter. Only subjects with non-missing values were included in the analysis.</population>
          <units>responders</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="19"/>
                  </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>A responder was defined as a subject with at least one level decrease on the MAS scale.</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.2400</p_value>
            <p_value_desc>Based on a generalised linear model including factors for treatment, spasticity pattern, country and MAS baseline score.</p_value_desc>
            <method>Generalised linear model</method>
            <param_type>Treatment difference</param_type>
            <param_value>-0.1324</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.3531</ci_lower_limit>
            <ci_upper_limit>0.0884</ci_upper_limit>
            <estimate_desc>Difference of the two clinical success rates (NMJ Targeted minus Current Clinical Practice).</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline of Spasticity Related Pain Measured by Visual Analogue Scale (VAS), Assessed by the Subject</title>
        <description>Pain assessment using the VAS. The VAS was a 10 cm straight horizontal line scoring scale. Score range on VAS was from 0 to 10 where 0 indicated no pain and 10 indicated worst pain imaginable.</description>
        <time_frame>Baseline, Week 4 and Week 12</time_frame>
        <population>ITT population: all treated subjects having at least one Baseline assessment of the primary efficacy parameter.&#xD;
CCP=Current Clinical Practice; N'=number of subjects with data at each time point for each treatment group; NMJ=neuromuscular junction.</population>
        <group_list>
          <group group_id="O1">
            <title>NMJ Targeted</title>
            <description>NMJ targeted technique and low-concentration dilution (Dysport 100 U/mL): A single injection per muscle was given in the midline of the band of NMJ zones. With a Dysport dilution of 100 U/mL the volume to be injected varied between 0.4 mL and 2.0 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment.</description>
          </group>
          <group group_id="O2">
            <title>Current Clinical Practice</title>
            <description>Current clinical practice technique and high-concentration dilution (Dysport 300 U/mL): The same number and sites of injections/deposits per muscle were given as per prestudy. With a Dysport dilution of 300 U/mL the volume to be injected varied between 0.1 mL and 0.7 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline of Spasticity Related Pain Measured by Visual Analogue Scale (VAS), Assessed by the Subject</title>
          <description>Pain assessment using the VAS. The VAS was a 10 cm straight horizontal line scoring scale. Score range on VAS was from 0 to 10 where 0 indicated no pain and 10 indicated worst pain imaginable.</description>
          <population>ITT population: all treated subjects having at least one Baseline assessment of the primary efficacy parameter.&#xD;
CCP=Current Clinical Practice; N'=number of subjects with data at each time point for each treatment group; NMJ=neuromuscular junction.</population>
          <units>Change in VAS from Baseline</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="40"/>
                    <count group_id="O2" value="43"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.80" spread="23.07"/>
                    <measurement group_id="O2" value="-4.35" spread="12.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="39"/>
                    <count group_id="O2" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.03" spread="26.02"/>
                    <measurement group_id="O2" value="0.03" spread="20.67"/>
                  </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>Mean change in VAS from Baseline to Week 4.</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.9448</p_value>
            <method>ANOVA</method>
            <method_desc>Analysis of variance (ANOVA) included factors for treatment, spasticity pattern and country, and Baseline VAS as a covariate.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Mean change in VAS from Baseline to Week 12.</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.5458</p_value>
            <method>ANOVA</method>
            <method_desc>ANOVA included factors for treatment, spasticity pattern and country, and Baseline VAS as a covariate.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Injection Site Pain Measured by VAS at Day 1.</title>
        <description>Pain assessment using the VAS. The VAS was a 100 mm straight horizontal line scoring scale. Score range on VAS was from 0 to 100 where 0 indicated no pain and 100 indicated worst pain imaginable.</description>
        <time_frame>Baseline</time_frame>
        <population>ITT population: all treated subjects having at least one Baseline assessment of the primary efficacy parameter. Only subjects with non-missing values were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>NMJ Targeted</title>
            <description>NMJ targeted technique and low-concentration dilution (Dysport 100 U/mL): A single injection per muscle was given in the midline of the band of NMJ zones. With a Dysport dilution of 100 U/mL the volume to be injected varied between 0.4 mL and 2.0 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment.</description>
          </group>
          <group group_id="O2">
            <title>Current Clinical Practice</title>
            <description>Current clinical practice technique and high-concentration dilution (Dysport 300 U/mL): The same number and sites of injections/deposits per muscle were given as per prestudy. With a Dysport dilution of 300 U/mL the volume to be injected varied between 0.1 mL and 0.7 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Injection Site Pain Measured by VAS at Day 1.</title>
          <description>Pain assessment using the VAS. The VAS was a 100 mm straight horizontal line scoring scale. Score range on VAS was from 0 to 100 where 0 indicated no pain and 100 indicated worst pain imaginable.</description>
          <population>ITT population: all treated subjects having at least one Baseline assessment of the primary efficacy parameter. Only subjects with non-missing values were included in the analysis.</population>
          <units>mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.67" spread="25.37"/>
                    <measurement group_id="O2" value="30.68" spread="27.33"/>
                  </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>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.4006</p_value>
            <method>ANOVA</method>
            <method_desc>ANOVA included factors for treatment, spasticity pattern and country.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Achievement of the Primary Goal Measured by Goal Attainment Scale (GAS)</title>
        <description>At Baseline, an agreed primary goal related to elbow flexion in one of the following categories was determined: active function, impairment, involuntary movement, mobility, pain passive function or other. Each goal was usually rated -1, unless the subject was as bad as he/she could be in that particular goal area, in which case the Baseline score was -2. The evaluator rated the outcome score at Week 4 or Week 12, depending on the time point defined at the baseline visit (Visit 1), using the GAS five-point scale (-2, -1, 0, +1 and +2).</description>
        <time_frame>Up to Week 12</time_frame>
        <population>ITT population: all treated subjects having at least one Baseline assessment of the primary efficacy parameter. Only subjects with non-missing values were included in the analysis. Only overall GAS score data are summarised below.</population>
        <group_list>
          <group group_id="O1">
            <title>NMJ Targeted</title>
            <description>NMJ targeted technique and low-concentration dilution (Dysport 100 U/mL): A single injection per muscle was given in the midline of the band of NMJ zones. With a Dysport dilution of 100 U/mL the volume to be injected varied between 0.4 mL and 2.0 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment.</description>
          </group>
          <group group_id="O2">
            <title>Current Clinical Practice</title>
            <description>Current clinical practice technique and high-concentration dilution (Dysport 300 U/mL): The same number and sites of injections/deposits per muscle were given as per prestudy. With a Dysport dilution of 300 U/mL the volume to be injected varied between 0.1 mL and 0.7 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Achievement of the Primary Goal Measured by Goal Attainment Scale (GAS)</title>
          <description>At Baseline, an agreed primary goal related to elbow flexion in one of the following categories was determined: active function, impairment, involuntary movement, mobility, pain passive function or other. Each goal was usually rated -1, unless the subject was as bad as he/she could be in that particular goal area, in which case the Baseline score was -2. The evaluator rated the outcome score at Week 4 or Week 12, depending on the time point defined at the baseline visit (Visit 1), using the GAS five-point scale (-2, -1, 0, +1 and +2).</description>
          <population>ITT population: all treated subjects having at least one Baseline assessment of the primary efficacy parameter. Only subjects with non-missing values were included in the analysis. Only overall GAS score data are summarised below.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Overall GAS score of -2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Overall GAS score of -1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Overall GAS score of 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Overall GAS score of +1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Overall GAS score of +2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </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>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.5747</p_value>
            <method>Mann-Whitney U-test</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Subject Global Evaluation of Treatment Effect</title>
        <description>Comparison of treatment effect between previous (prestudy) and study treatment cycles assessed by the subject at the end of study (Week 12 up to Week 24 (Visit 3 or Visit 4)). Categorised as follows: Much worse / Worse / Same / Better / Much better.</description>
        <time_frame>Up to Week 24</time_frame>
        <population>ITT population: all treated subjects having at least one Baseline assessment of the primary efficacy parameter. Only subjects with non-missing values were included in the analysis. If a subject had more than one evaluation entry, the last one was used.</population>
        <group_list>
          <group group_id="O1">
            <title>NMJ Targeted</title>
            <description>NMJ targeted technique and low-concentration dilution (Dysport 100 U/mL): A single injection per muscle was given in the midline of the band of NMJ zones. With a Dysport dilution of 100 U/mL the volume to be injected varied between 0.4 mL and 2.0 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment.</description>
          </group>
          <group group_id="O2">
            <title>Current Clinical Practice</title>
            <description>Current clinical practice technique and high-concentration dilution (Dysport 300 U/mL): The same number and sites of injections/deposits per muscle were given as per prestudy. With a Dysport dilution of 300 U/mL the volume to be injected varied between 0.1 mL and 0.7 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Subject Global Evaluation of Treatment Effect</title>
          <description>Comparison of treatment effect between previous (prestudy) and study treatment cycles assessed by the subject at the end of study (Week 12 up to Week 24 (Visit 3 or Visit 4)). Categorised as follows: Much worse / Worse / Same / Better / Much better.</description>
          <population>ITT population: all treated subjects having at least one Baseline assessment of the primary efficacy parameter. Only subjects with non-missing values were included in the analysis. If a subject had more than one evaluation entry, the last one was used.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Much Better</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Better</title>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No Change From Baseline</title>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                    <measurement group_id="O2" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Worse</title>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Much Worse</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </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>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.1802</p_value>
            <method>Mann-Whitney U-test</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Investigator Preference of Injection Technique</title>
        <description>When all patients at the site had completed the study (last subject last visit) a global assessment of the injection technique was to be made by the Investigators. The following question was answered: &quot;Based on your experience during this study, which injection technique do you prefer?&quot;</description>
        <time_frame>Following last visit of the last subject at each site</time_frame>
        <population>The question on preferred injection technique was answered by 3 of the 20 Investigators.</population>
        <group_list>
          <group group_id="O1">
            <title>Number of Investigators Who Responded</title>
            <description>Investigator preference for using the NMJ Targeted versus the Current Clinical Practice technique was requested at each of the 20 sites (20 Investigators).</description>
          </group>
        </group_list>
        <measure>
          <title>Investigator Preference of Injection Technique</title>
          <description>When all patients at the site had completed the study (last subject last visit) a global assessment of the injection technique was to be made by the Investigators. The following question was answered: &quot;Based on your experience during this study, which injection technique do you prefer?&quot;</description>
          <population>The question on preferred injection technique was answered by 3 of the 20 Investigators.</population>
          <units>Investigators</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>NMJ Targeted</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Current Clinical Practice</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events (AEs) were monitored from informed consent to the time when the subject's participation in the study ended (Week 12 to Week 24 (Visit 3 or Visit 4)). AEs were elicited by direct, non-leading questioning at each clinic visit or by spontaneous reports.</time_frame>
      <desc>The safety population was defined as all subjects who received at least one dose of study medication. The safety population was analysed using subjects as treated. If a subject experienced more than one event in a System Organ Class (SOC), the subject was counted only once in that SOC.</desc>
      <group_list>
        <group group_id="E1">
          <title>NMJ Targeted</title>
          <description>NMJ targeted technique and low-concentration dilution (Dysport 100 U/mL): A single injection per muscle was given in the midline of the band of NMJ zones. With a Dysport dilution of 100 U/mL the volume to be injected varied between 0.4 mL and 2.0 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment.</description>
        </group>
        <group group_id="E2">
          <title>Current Clinical Practice</title>
          <description>Current clinical practice technique and high-concentration dilution (Dysport 300 U/mL): The same number and sites of injections/deposits per muscle were given as per prestudy. With a Dysport dilution of 300 U/mL the volume to be injected varied between 0.1 mL and 0.7 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment .</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 15.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Femoral neck fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Epilepsy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 15.0</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="13" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Injection site hypersensitivity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Eye infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Muscle strain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Bursitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </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="44"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Epilepsy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Neuralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Migraine</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Epididymitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Acquired hydrocele</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain of skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="44"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The Sponsor required reasonable opportunity to review any abstract, presentation or paper before the material was submitted for publication or communicated. This also applied to any amendments that were requested by referees or journal editors. The Sponsor committed to comment on the draft documents within the time period agreed in the contractual arrangements between the Sponsor and authors or their institution. Delays were also possible if publication would adversely affect patentability.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Due to slow recruitment, the study was terminated early. Therefore, fewer subjects than planned were enrolled.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Medical Director, Neurology</name_or_title>
      <organization>Ipsen</organization>
      <phone>clinicaltrials@ipsen.com</phone>
      <email>clinicaltrials@ipsen.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/NCT01682148
org study id: A-99-52120-162
secondary id: 2011-005375-16
nct id: NCT01682148
lead sponsor: 
has dmc: No
The aim of the study was to compare Dysport treatment results (as assessed by Modified
      Ashworth Scale (MAS) in the elbow joint 4 weeks post treatment) following two treatment
      techniques: the current clinical practice injection technique using high-concentration
      dilution (300 U/mL Dysport) versus the neuromuscular junction (NMJ)-targeted injection
      technique using low-concentration dilution (100 U/mL Dysport). The hypothesis was that one
      high-volume, low-concentration injection located centrally in the area/band of the NMJ zones
      would be as effective as the technique used in current medical practice.
This was a randomised, evaluator-blinded, comparative, parallel group, multicentre study,
      conducted in four countries (Denmark, Finland, Norway and Sweden). For each subject, the
      primary efficacy assessments using MAS were performed by the same blinded evaluator, and
      every effort was made at each site to ensure that the MAS evaluator was the same person
      throughout the study. Dysport doses were to follow clinical practice for subjects suffering
      from upper limb spasticity position pattern type 1, 3 or 4 post stroke or traumatic brain
      injury.

      The hypothesis for this study was that one low-concentration botulinum neurotoxin type A
      (BoNT-A) injection per muscle, centrally located in the area/band of the NMJ zones, would
      spread to and block the surrounding NMJ zones and be as effective as the technique used today
      in clinical practice. The possibility to reduce the number of injection points would decrease
      the risk of injection discomfort, pain and injection site bleeding for the patient. A
      simplified injection technique with one injection per muscle and in a defined location would
      also benefit physicians.

      At Baseline (Visit 1), subjects were randomised to one of two treatment groups:

        -  Group 1: Current clinical practice technique and high-concentration dilution: Dysport
           300 U/mL.

        -  Group 2: NMJ targeted technique and low-concentration dilution: Dysport 100 U/mL.

      Each subject visited the clinic on at least three occasions:

        -  Baseline (Visit 1): Screening, randomisation and Dysport treatment.

        -  Week 4 (Visit 2): Treatment follow-up, 4 weeks after Dysport treatment.

        -  Week 12 (Visit 3): Treatment and study follow-up, 12 weeks after Dysport treatment.

      For subjects not receiving any post study BoNT-A injection at Week 12 due to remaining
      treatment effect, an extra visit (Visit 4) for study follow-up was to take place at the next
      routine visit planned for a new BoNT-A injection, at the latest 24 weeks post study
      injection.

      The duration of each subject's study period was at a minimum 12 weeks and maximum 24 weeks.
      The overall duration of the study was planned to be approximately 36 months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Change From Baseline for Elbow Flexors Muscle Tone as Measured by the Modified Ashworth Scale (MAS) at Week 4
time frame: Baseline to Week 4
description: A clinically relevant change was one level decrease on the MAS scale. Subjects meeting the defined decrease at Week 4 were considered as responders in the primary efficacy analysis.
measure: Change From Baseline for Elbow Flexors Muscle Tone as Measured by the Modified Ashworth Scale (MAS) at Week 4 and Week 12
time frame: Baseline to Week 12
description: Increased muscle tone in elbow flexors was assessed using the MAS. Scale ranges from 0 (no increase in muscle tone) to 4 (affected part rigid in flexion or extension).
measure: Change From Baseline for Elbow Flexors Muscle Tone as Measured by the MAS at Week 12
time frame: Baseline to Week 12
description: A clinically relevant change was one level decrease on the MAS scale. Subjects meeting the defined decrease at Week 12 were considered as responders.
measure: Change From Baseline of Spasticity Related Pain Measured by Visual Analogue Scale (VAS), Assessed by the Subject
time frame: Baseline, Week 4 and Week 12
description: Pain assessment using the VAS. The VAS was a 10 cm straight horizontal line scoring scale. Score range on VAS was from 0 to 10 where 0 indicated no pain and 10 indicated worst pain imaginable.
measure: Injection Site Pain Measured by VAS at Day 1.
time frame: Baseline
description: Pain assessment using the VAS. The VAS was a 100 mm straight horizontal line scoring scale. Score range on VAS was from 0 to 100 where 0 indicated no pain and 100 indicated worst pain imaginable.
measure: Achievement of the Primary Goal Measured by Goal Attainment Scale (GAS)
time frame: Up to Week 12
description: At Baseline, an agreed primary goal related to elbow flexion in one of the following categories was determined: active function, impairment, involuntary movement, mobility, pain passive function or other. Each goal was usually rated -1, unless the subject was as bad as he/she could be in that particular goal area, in which case the Baseline score was -2. The evaluator rated the outcome score at Week 4 or Week 12, depending on the time point defined at the baseline visit (Visit 1), using the GAS five-point scale (-2, -1, 0, +1 and +2).
measure: Subject Global Evaluation of Treatment Effect
time frame: Up to Week 24
description: Comparison of treatment effect between previous (prestudy) and study treatment cycles assessed by the subject at the end of study (Week 12 up to Week 24 (Visit 3 or Visit 4)). Categorised as follows: Much worse / Worse / Same / Better / Much better.
measure: Investigator Preference of Injection Technique
time frame: Following last visit of the last subject at each site
description: When all patients at the site had completed the study (last subject last visit) a global assessment of the injection technique was to be made by the Investigators. The following question was answered: "Based on your experience during this study, which injection technique do you prefer?"
arm group label: NMJ Targeted
arm group type: Experimental
description: NMJ targeted technique and low-concentration dilution (Dysport 100 U/mL). The same number and sites of injections/deposits per muscle were given as per prestudy. With a Dysport dilution of 300 U/mL the volume to be injected varied between 0.1 mL and 0.7 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment.
arm group label: Current Clinical Practice
arm group type: Active Comparator
description: Current clinical practice technique and high-concentration dilution (Dysport 300 U/mL).
A single injection per muscle was given in the midline of the band of NMJ zones. With a Dysport dilution of 100 U/mL the volume to be injected varied between 0.4 mL and 2.0 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment.
intervention type: Biological
intervention name: Botulinum toxin type A
arm group label: Current Clinical Practice
arm group label: NMJ Targeted
other name: AbobotulinumtoxinA (Dysport®)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ipsen Medical Director
role: Study Director
affiliation: Ipsen
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country: Denmark
country: Finland
country: Norway
country: Sweden
responsible party type: Sponsor
mesh term: Muscle Spasticity
mesh term: Botulinum Toxins
mesh term: Botulinum Toxins, Type A
mesh term: abobotulinumtoxinA
sharing ipd: Yes
ipd description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized, and study documents will be redacted to protect the privacy of study participants.
Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.
ipd time frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
ipd access criteria: Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).
ipd url: https://vivli.org/members/ourmembers/
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Due to slow recruitment, the study was terminated early. Therefore, fewer subjects than planned were enrolled.
point of contact: 