<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/NCT03753763</url>
  </required_header>
  <id_info>
    <org_study_id>Z7219K01</org_study_id>
    <secondary_id>2018-004145-16</secondary_id>
    <nct_id>NCT03753763</nct_id>
  </id_info>
  <brief_title>Safinamide for Multiple System Atrophy (MSA)</brief_title>
  <official_title>12-weeks, Multicentre, Randomized, Double-blind, Placebo-controlled, Exploratory, Pilot Study to Evaluate the Safety and Efficacy of Safinamide 200 mg OD, as add-on Therapy, in Patients With Possible or Probable Parkinsonian Variant of MSA</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zambon SpA</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Zambon SpA</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study is a placebo controlled study, with two parallel arms, in which participants will&#xD;
      be randomly assigned in a 2:1 ratio to receive either active (200 mg safinamide) or placebo&#xD;
      in a double blind manner. Study population is patients diagnosed, with possible or probable&#xD;
      parkinsonian variant of Multiple System Atrophy who are on a stable treatment of levodopa&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The overall design is a parallel group, placebo controlled, double blind study. The target&#xD;
      population are participants diagnosed with possible or probable parkinsonian variant of&#xD;
      Multiple System Atrophy who are on stable doses of levodopa.&#xD;
&#xD;
      Trial participation will be up to a maximum duration of 14 weeks and will comprise a&#xD;
      screening period (up to 2 weeks), a 2-week run in period during which subjects will receive 1&#xD;
      tablet (either 100 mg safinamide or matching placebo), followed by a 10-week period, during&#xD;
      which study participants will take 2 tablets of study medication (200 mg safinamide or&#xD;
      placebo) once daily, taken in the morning in addition to their morning levodopa dose. A&#xD;
      telephone follow-up call will be performed 2 weeks after the end of treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 29, 2019</start_date>
  <completion_date type="Actual">January 5, 2021</completion_date>
  <primary_completion_date type="Actual">January 5, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>TEAEs (Treatment Emergent Adverse Events) and SAEs (Serious Adverse Events)</measure>
    <time_frame>Throughout the study, from baseline (and at each interim visit) to telephone follow-up visit at 14 week.</time_frame>
    <description>While evaluating safety and tolerability of safinamide, 200 mg od, compared with placebo, severity of TEAEs, their relationship to study drug, their seriousness and their consequences were assessed. TEAEs were defined as adverse events (AEs) that started after the first dose of study drug.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 12 in the Goniometric Measurement for Anterior Displacement</measure>
    <time_frame>From baseline to week 12</time_frame>
    <description>To evaluate the potential efficacy of safinamide 200 mg od, as add-on therapy, on quality of life (change in anterior displacement). The goniometric measurement consists in the posture evaluation of the patient, measuring through a goniometer the angle of the flexion of the trunk. Goniometric measurement of &quot;anterior&quot; displacement was determined using a wall goniometer and expressing the value in degrees in the range of 0 to 90.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 12 in the Goniometric Measurement for Lateral Displacement</measure>
    <time_frame>From baseline to week 12</time_frame>
    <description>To evaluate the potential efficacy of safinamide 200 mg od, as add-on therapy, on quality of life (change in anterior displacement). The goniometric measurement consists in the posture evaluation of the patient, measuring through a goniometer the angle of the flexion of the trunk. Goniometric measurement of &quot;lateral&quot; displacement was determined using a wall goniometer and expressing the value in degrees in the range of 0 to 90.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 12 in Unified Multiple System Atrophy Rating Scale (UMSARS), Part II (ITT Population)</measure>
    <time_frame>From baseline to week 12</time_frame>
    <description>UMSARS is a validated, disease-specific scale representing the diverse signs and symptoms in MSA. Higher scores on the UMSARS scales mean poorer health.&#xD;
UMSARS has the following domains:&#xD;
Part I - Activities of Daily Living score (12 questions ranged in 0-4 [total score 0-48]) that evaluates motor including autonomic activities Part II - Motor Examination score (14 questions, [total score 0-56]) Part III - Autonomic Examination Part IV - Global disability scale ((1=completely independent; 2=not completely independent; 3=more dependent; 4=very dependent; 5=total dependent and helpless).&#xD;
Only UMSARS Part II total score is reported, which was obtained as the sum of the 14 items in the scale. If any of the items were missing, then the total score was considered missing. Higher scores indicate worse functional situation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 12 in Unified Multiple System Atrophy Rating Scale (UMSARS), Part II (PP Population)</measure>
    <time_frame>From baseline to week 12</time_frame>
    <description>UMSARS is a validated, disease-specific scale representing the diverse signs and symptoms in MSA. Higher scores on the UMSARS scales mean poorer health.&#xD;
UMSARS has the following domains:&#xD;
Part I - Activities of Daily Living score (12 questions ranged in 0-4 [total score 0-48]) that evaluates motor including autonomic activities Part II - Motor Examination score (14 questions, [total score 0-56]) Part III - Autonomic Examination Part IV - Global disability scale ((1=completely independent; 2=not completely independent; 3=more dependent; 4=very dependent; 5=total dependent and helpless).&#xD;
Only UMSARS Part II total score is reported, which was obtained as the sum of the 14 items in the scale. If any of the items were missing, then the total score was considered missing. Higher scores indicate worse functional situation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 12 in Multiple System Atrophy Health-Related Quality of Life (MSA-QoL) Scale</measure>
    <time_frame>From baseline to week 12</time_frame>
    <description>The MSA-QoL is a self-reported questionnaire focusing on MSA-specific symptoms and has a scale ranging from 0 to 160, with 0= 'no problem' and 160= &quot;extreme problem&quot;.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 12 in Montreal Cognitive Assessment (MoCA) Scale</measure>
    <time_frame>From baseline to week 12</time_frame>
    <description>The Montreal Cognitive Assessment (MoCA) was designed as a tool for rapid screening for mild cognitive impairment. It evaluates different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructive skills, abstraction, calculation and orientation. The administration time of the MoCa is 10 minutes. The MoCA scale ranges from 0 to 30, with higher scores indicating better cognitive functioning.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 12 in Unified Dystonia Rating Scale (UDRS)</measure>
    <time_frame>From baseline to week 12</time_frame>
    <description>UDRS consists of a Historical Section, divided into questionnaires about 1) on-dyskinesia and 2) off -dystonia, and an Objective Section, divided into 3) impairment and 4) disability scales. The Historical Section is scored from 0-60, and the Objective section is scored 0-44, where higher scores reflect greater difficulty or impairment.&#xD;
The Unified Dystonia Rating Scale (UDRS) assesses the motor severity and duration of dystonia in 14 body areas. The total score, obtained as the sum of the severity and duration factors, ranges from 0 to 112. Higher scores indicate worse dystonia.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">49</enrollment>
  <condition>Multiple System Atrophy</condition>
  <arm_group>
    <arm_group_label>Active</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Safinamide methanesulfonate film-coated tablets once daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Safinamide Methanesulfonate matching placebo film-coated tablets once daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Safinamide Methanesulfonate</intervention_name>
    <description>100 mg (free base)</description>
    <arm_group_label>Active</arm_group_label>
    <other_name>Xadago</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Safinamide Methanesulfonate matching placebo</intervention_name>
    <description>100 mg placebo</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Participant must be 30 to 80 years of age inclusive, at the time of signing the&#xD;
             informed consent;&#xD;
&#xD;
          2. Participants who are diagnosed (with MRI confirmation) with possible or probable&#xD;
             parkinsonian variant of Multiple System Atrophy less than 2 years ago;&#xD;
&#xD;
          3. Participants with an anticipated survival of at least 3 years in the opinion of the&#xD;
             investigator;&#xD;
&#xD;
          4. Female not pregnant, not breastfeeding, and at least one of the following conditions&#xD;
             applies:&#xD;
&#xD;
               -  Not a woman of childbearing potential OR&#xD;
&#xD;
               -  A woman of childbearing potential who agrees to follow the contraceptive guidance&#xD;
                  during the treatment period and for at least 30 days after the last dose of study&#xD;
                  intervention;&#xD;
&#xD;
          5. Capable of giving signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of neurosurgical procedure, including stereotactic surgery;&#xD;
&#xD;
          2. History of Deep Brain Stimulation (DBS);&#xD;
&#xD;
          3. History of bipolar disorder, severe depression, schizophrenia or other psychotic&#xD;
             disorder;&#xD;
&#xD;
          4. History of drug and/or alcohol abuse within 12 months prior to screening as defined by&#xD;
             the current edition of the Diagnostic and Statistical Manual of Mental Disorders;&#xD;
&#xD;
          5. History of dementia (DSM-V criteria);&#xD;
&#xD;
          6. Ophthalmologic history including any of the following conditions: albinism, uveitis,&#xD;
             retinitis pigmentosa, retinal degeneration, active retinopathy, severe progressive&#xD;
             diabetic retinopathy, inherited retinopathy or family history of hereditary retinal&#xD;
             disease;&#xD;
&#xD;
          7. Active hepatitis B or C;&#xD;
&#xD;
          8. History of human immunodeficiency virus (HIV) infection;&#xD;
&#xD;
          9. Subjects not able to swallow oral medications;&#xD;
&#xD;
         10. Subjects with severe orthostatic symptoms;&#xD;
&#xD;
         11. Impaired ambulation, i.e. falling more than once per week, bedridden patients or&#xD;
             confined to a wheelchair during the whole day;&#xD;
&#xD;
         12. Subjects with active malignant neoplasms;&#xD;
&#xD;
         13. Movement disorders other than MSA (e.g. Parkinson Disease, dementia with Lewy bodies,&#xD;
             essential tremor, progressive supranuclear palsy, pharmacological or post-encephalic&#xD;
             parkinsonism);&#xD;
&#xD;
         14. Any clinically significant or unstable medical or surgical condition that, in the&#xD;
             opinion of the investigator, might preclude safe completion of the study or might&#xD;
             affect the results of the study;&#xD;
&#xD;
         15. Not on a stable regime, for at least 4 weeks prior to the randomization (baseline&#xD;
             visit), of&#xD;
&#xD;
               1. oral levodopa (including controlled release, immediate release or a combination&#xD;
                  of controlled release/immediate release), with or without benserazide/carbidopa,&#xD;
                  with or without addition of a catechol O-methyltransferase (COMT) inhibitor or&#xD;
&#xD;
               2. dopamine agonist, anticholinergic and/or amantadine.&#xD;
&#xD;
         16. Patients should not have received treatment with monoamine oxidase inhibitors in the 2&#xD;
             weeks prior to the randomization visit, nor treatment with levodopa infusion,&#xD;
             pethidine, opiates, opioids, fluoxetine, fluvoxamine in the 4 weeks prior to the&#xD;
             randomization visit;&#xD;
&#xD;
         17. Patients should not have received treatment with an oral or depot neuroleptic within&#xD;
             12 weeks prior to the randomization visit;&#xD;
&#xD;
         18. Use of any investigational drug within 30 days prior to screening or 5 half-lives,&#xD;
             whichever is the longest;&#xD;
&#xD;
         19. Montreal Cognitive Assessment (MoCA) ≤ 20;&#xD;
&#xD;
         20. Laboratory assessments showing moderate or severe hepatic impairment (2x ULN);&#xD;
&#xD;
         21. Allergy/sensitivity or contraindications to the investigational medicinal products&#xD;
             (IMPs) or their excipients, anticonvulsants, levodopa or other anti-parkinsonian&#xD;
             drugs;&#xD;
&#xD;
         22. Any clinically significant condition which, in the opinion of the Investigator, would&#xD;
             not be compatible with study participation or represent a risk for patients while in&#xD;
             the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Charlotte Keywood, MD</last_name>
    <role>Study Director</role>
    <affiliation>Zambon SpA</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Università di Bologna</name>
      <address>
        <city>Bologna</city>
        <zip>40123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AAST degli Spedali Civili di Brescia</name>
      <address>
        <city>Brescia</city>
        <zip>25123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>San Raffaele Cassino</name>
      <address>
        <city>Cassino</city>
        <zip>03043</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione Università &quot;G. D'Annunzio&quot;</name>
      <address>
        <city>Chieti</city>
        <zip>66013</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS Istituto Neurologico Carlo Besta</name>
      <address>
        <city>Milano</city>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria - Università degli Studi della Campania Luigi Vanvitelli</name>
      <address>
        <city>Napoli</city>
        <zip>80138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera di Padova</name>
      <address>
        <city>Padova</city>
        <zip>35128</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Opsedaliero Universitaria Pisana</name>
      <address>
        <city>Pisa</city>
        <zip>56126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Clinico Humanitas</name>
      <address>
        <city>Rozzano</city>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria OO.RR. San Giovanni di Dio - Ruggi d'Aragona</name>
      <address>
        <city>Salerno</city>
        <zip>84131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Santa Maria di Terni</name>
      <address>
        <city>Terni</city>
        <zip>05100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario de Elche</name>
      <address>
        <city>Alicante</city>
        <zip>03203</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Cruces</name>
      <address>
        <city>Barakaldo</city>
        <zip>48903</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de la Santa Creu i Sant Pau Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>08025</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Gregorio Maranon</name>
      <address>
        <city>Madrid</city>
        <zip>28007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Puerta de Hierro Majadahonda</name>
      <address>
        <city>Madrid</city>
        <zip>28222</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Ramon y Cajal</name>
      <address>
        <city>Madrid</city>
        <zip>28304</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen Macarena</name>
      <address>
        <city>Sevilla</city>
        <zip>41009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen de Rocio</name>
      <address>
        <city>Sevilla</city>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
    <country>Spain</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>November 19, 2018</study_first_submitted>
  <study_first_submitted_qc>November 22, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 27, 2018</study_first_posted>
  <results_first_submitted>July 7, 2021</results_first_submitted>
  <results_first_submitted_qc>July 29, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">August 24, 2021</results_first_posted>
  <last_update_submitted>October 8, 2021</last_update_submitted>
  <last_update_submitted_qc>October 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 13, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>MSA, safinamide</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple System Atrophy</mesh_term>
    <mesh_term>Shy-Drager Syndrome</mesh_term>
    <mesh_term>Atrophy</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 13, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/63/NCT03753763/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 20, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/63/NCT03753763/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Approximately 56 participants were planned to be screened in order to achieve 49 participants randomly assigned (2:1) to study drug and 42 evaluable participants, resulting in a planned estimated total of 32 evaluable participants receiving safinamide and 17 evaluable participants receiving matching placebo. Only 42 completed the study while 7 discontinued it.</recruitment_details>
      <pre_assignment_details>Participants (males and females between 30 and 80 years) diagnosed with possible or probable parkinsonian variant of MSA &lt;2 years before, with MRI consistent with the diagnosis of MSA, and not suggesting an alternative explanation to the clinical diagnosis of MSA, and with an anticipated survival of at least 3 years in the opinion of the Investigator.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Safinamide</title>
          <description>Safinamide methanesulfonate film-coated tablets once daily. During the titration period of 2 weeks (Week 1 to Week 2) participants received 1 tablet (100 mg) safinamide, while during the treatment period (Week 3 to Week 12) they received 2 tablets (200 mg) safinamide once-a-day, taken in the morning, in addition to their daily levodopa dose.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Safinamide methanesulfonate matching placebo film-coated tablets once daily. Safinamide matching placebo was administered both during the titration period of 2 weeks (Week 1 to Week 2) and during the following period (Week 3 to Week 12), once daily, taken in the morning, in addition to their daily levodopa dose.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="32"/>
                <participants group_id="P2" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>clinical deterioration</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The ITT Population included all randomized participants. This population was used for describing all the demographic characteristics and all efficacy variables.</population>
      <group_list>
        <group group_id="B1">
          <title>Safinamide</title>
          <description>Safinamide methanesulfonate film-coated tablets once daily. During the titration period of 2 weeks (Week 1 to Week 2) participants received 1 tablet (100 mg) safinamide, while during the treatment period (Week 3 to Week 12) they received 2 tablets (200 mg) safinamide once-a-day, taken in the morning, in addition to their daily levodopa dose.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Safinamide methanesulfonate matching placebo film-coated tablets once daily. Safinamide matching placebo was administered both during the titration period of 2 weeks (Week 1 to Week 2) and during the following period (Week 3 to Week 12), once daily, taken in the morning, in addition to their daily levodopa dose.</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="32"/>
            <count group_id="B2" value="17"/>
            <count group_id="B3" value="49"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="65.8" spread="8.23"/>
                    <measurement group_id="B2" value="62.8" spread="10.27"/>
                    <measurement group_id="B3" value="64.7" spread="9.00"/>
                  </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="20"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="48"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Italy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Spain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>TEAEs (Treatment Emergent Adverse Events) and SAEs (Serious Adverse Events)</title>
        <description>While evaluating safety and tolerability of safinamide, 200 mg od, compared with placebo, severity of TEAEs, their relationship to study drug, their seriousness and their consequences were assessed. TEAEs were defined as adverse events (AEs) that started after the first dose of study drug.</description>
        <time_frame>Throughout the study, from baseline (and at each interim visit) to telephone follow-up visit at 14 week.</time_frame>
        <population>The Safety Population included all randomized participants who took at least 1 dose of study drug. This population was used to summarize all safety data.</population>
        <group_list>
          <group group_id="O1">
            <title>Safinamide</title>
            <description>Safinamide methanesulfonate film-coated tablets once daily. During the titration period of 2 weeks (Week 1 to Week 2) participants received 1 tablet (100 mg) safinamide, while during the treatment period (Week 3 to Week 12) they received 2 tablets (200 mg) safinamide once-a-day, taken in the morning, in addition to their daily levodopa dose.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Safinamide methanesulfonate matching placebo film-coated tablets once daily. Safinamide matching placebo was administered both during the titration period of 2 weeks (Week 1 to Week 2) and during the following period (Week 3 to Week 12), once daily, taken in the morning, in addition to their daily levodopa dose.</description>
          </group>
        </group_list>
        <measure>
          <title>TEAEs (Treatment Emergent Adverse Events) and SAEs (Serious Adverse Events)</title>
          <description>While evaluating safety and tolerability of safinamide, 200 mg od, compared with placebo, severity of TEAEs, their relationship to study drug, their seriousness and their consequences were assessed. TEAEs were defined as adverse events (AEs) that started after the first dose of study drug.</description>
          <population>The Safety Population included all randomized participants who took at least 1 dose of study drug. This population was used to summarize all safety data.</population>
          <units>events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52"/>
                    <measurement group_id="O2" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mild TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49"/>
                    <measurement group_id="O2" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Moderate TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Severe TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Study drug-related TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs leading to study drug withdrawal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AEs leading to death</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 12 in the Goniometric Measurement for Anterior Displacement</title>
        <description>To evaluate the potential efficacy of safinamide 200 mg od, as add-on therapy, on quality of life (change in anterior displacement). The goniometric measurement consists in the posture evaluation of the patient, measuring through a goniometer the angle of the flexion of the trunk. Goniometric measurement of &quot;anterior&quot; displacement was determined using a wall goniometer and expressing the value in degrees in the range of 0 to 90.</description>
        <time_frame>From baseline to week 12</time_frame>
        <population>The ITT Population included all randomized participants. This population was used for all efficacy variables.</population>
        <group_list>
          <group group_id="O1">
            <title>Safinamide</title>
            <description>Safinamide methanesulfonate film-coated tablets once daily. During the titration period of 2 weeks (Week 1 to Week 2) participants received 1 tablet (100 mg) safinamide, while during the treatment period (Week 3 to Week 12) they received 2 tablets (200 mg) safinamide once-a-day, taken in the morning, in addition to their daily levodopa dose.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Safinamide methanesulfonate matching placebo film-coated tablets once daily. Safinamide matching placebo was administered both during the titration period of 2 weeks (Week 1 to Week 2) and during the following period (Week 3 to Week 12), once daily, taken in the morning, in addition to their daily levodopa dose.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 12 in the Goniometric Measurement for Anterior Displacement</title>
          <description>To evaluate the potential efficacy of safinamide 200 mg od, as add-on therapy, on quality of life (change in anterior displacement). The goniometric measurement consists in the posture evaluation of the patient, measuring through a goniometer the angle of the flexion of the trunk. Goniometric measurement of &quot;anterior&quot; displacement was determined using a wall goniometer and expressing the value in degrees in the range of 0 to 90.</description>
          <population>The ITT Population included all randomized participants. This population was used for all efficacy variables.</population>
          <units>degrees</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.3" spread="9.46"/>
                    <measurement group_id="O2" value="0.9" spread="8.01"/>
                  </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>The model included treatment, week of visit, and treatment-by-visit interaction as fixed effects and baseline score as a covariate.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.9697</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>A mixed-model repeated measures (MMRM) was used to analyze the change in anterior and lateral displacement from baseline</method_desc>
            <param_type>Least square mean difference</param_type>
            <param_value>0.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-6.3</ci_lower_limit>
            <ci_upper_limit>6.5</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 12 in the Goniometric Measurement for Lateral Displacement</title>
        <description>To evaluate the potential efficacy of safinamide 200 mg od, as add-on therapy, on quality of life (change in anterior displacement). The goniometric measurement consists in the posture evaluation of the patient, measuring through a goniometer the angle of the flexion of the trunk. Goniometric measurement of &quot;lateral&quot; displacement was determined using a wall goniometer and expressing the value in degrees in the range of 0 to 90.</description>
        <time_frame>From baseline to week 12</time_frame>
        <population>The ITT Population included all randomized participants. This population was used for all efficacy variables.</population>
        <group_list>
          <group group_id="O1">
            <title>Safinamide</title>
            <description>Safinamide methanesulfonate film-coated tablets once daily. During the titration period of 2 weeks (Week 1 to Week 2) participants received 1 tablet (100 mg) safinamide, while during the treatment period (Week 3 to Week 12) they received 2 tablets (200 mg) safinamide once-a-day, taken in the morning, in addition to their daily levodopa dose.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Safinamide methanesulfonate matching placebo film-coated tablets once daily. Safinamide matching placebo was administered both during the titration period of 2 weeks (Week 1 to Week 2) and during the following period (Week 3 to Week 12), once daily, taken in the morning, in addition to their daily levodopa dose.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 12 in the Goniometric Measurement for Lateral Displacement</title>
          <description>To evaluate the potential efficacy of safinamide 200 mg od, as add-on therapy, on quality of life (change in anterior displacement). The goniometric measurement consists in the posture evaluation of the patient, measuring through a goniometer the angle of the flexion of the trunk. Goniometric measurement of &quot;lateral&quot; displacement was determined using a wall goniometer and expressing the value in degrees in the range of 0 to 90.</description>
          <population>The ITT Population included all randomized participants. This population was used for all efficacy variables.</population>
          <units>degrees</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.3" spread="5.08"/>
                    <measurement group_id="O2" value="-0.2" spread="4.47"/>
                  </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>The model included treatment, week of visit, and treatment-by-visit interaction as fixed effects and baseline score as a covariate</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.7751</p_value>
            <p_value_desc>A mixed-model repeated measures (MMRM) was used to analyze the change in anterior and lateral displacement from baseline.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>least square mean difference</param_type>
            <param_value>0.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.1</ci_lower_limit>
            <ci_upper_limit>4.1</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 12 in Unified Multiple System Atrophy Rating Scale (UMSARS), Part II (ITT Population)</title>
        <description>UMSARS is a validated, disease-specific scale representing the diverse signs and symptoms in MSA. Higher scores on the UMSARS scales mean poorer health.&#xD;
UMSARS has the following domains:&#xD;
Part I - Activities of Daily Living score (12 questions ranged in 0-4 [total score 0-48]) that evaluates motor including autonomic activities Part II - Motor Examination score (14 questions, [total score 0-56]) Part III - Autonomic Examination Part IV - Global disability scale ((1=completely independent; 2=not completely independent; 3=more dependent; 4=very dependent; 5=total dependent and helpless).&#xD;
Only UMSARS Part II total score is reported, which was obtained as the sum of the 14 items in the scale. If any of the items were missing, then the total score was considered missing. Higher scores indicate worse functional situation.</description>
        <time_frame>From baseline to week 12</time_frame>
        <population>The ITT Population included all randomized participants. This population was used for all efficacy variables.</population>
        <group_list>
          <group group_id="O1">
            <title>Safinamide</title>
            <description>Safinamide methanesulfonate film-coated tablets once daily. During the titration period of 2 weeks (Week 1 to Week 2) participants received 1 tablet (100 mg) safinamide, while during the treatment period (Week 3 to Week 12) they received 2 tablets (200 mg) safinamide once-a-day, taken in the morning, in addition to their daily levodopa dose.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Safinamide methanesulfonate matching placebo film-coated tablets once daily. Safinamide matching placebo was administered both during the titration period of 2 weeks (Week 1 to Week 2) and during the following period (Week 3 to Week 12), once daily, taken in the morning, in addition to their daily levodopa dose.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 12 in Unified Multiple System Atrophy Rating Scale (UMSARS), Part II (ITT Population)</title>
          <description>UMSARS is a validated, disease-specific scale representing the diverse signs and symptoms in MSA. Higher scores on the UMSARS scales mean poorer health.&#xD;
UMSARS has the following domains:&#xD;
Part I - Activities of Daily Living score (12 questions ranged in 0-4 [total score 0-48]) that evaluates motor including autonomic activities Part II - Motor Examination score (14 questions, [total score 0-56]) Part III - Autonomic Examination Part IV - Global disability scale ((1=completely independent; 2=not completely independent; 3=more dependent; 4=very dependent; 5=total dependent and helpless).&#xD;
Only UMSARS Part II total score is reported, which was obtained as the sum of the 14 items in the scale. If any of the items were missing, then the total score was considered missing. Higher scores indicate worse functional situation.</description>
          <population>The ITT Population included all randomized participants. This population was used for all efficacy variables.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1" spread="5.40"/>
                    <measurement group_id="O2" value="-0.4" spread="5.85"/>
                  </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>The model included treatment, week of visit, and treatment-by-visit interaction as fixed effects and baseline score as a covariate.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.9076</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>A mixed-model repeated measures (MMRM) was used to analyze the change in from baseline in UMSARS Part II</method_desc>
            <param_type>least square mean difference</param_type>
            <param_value>0.2</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.3</ci_lower_limit>
            <ci_upper_limit>3.7</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 12 in Unified Multiple System Atrophy Rating Scale (UMSARS), Part II (PP Population)</title>
        <description>UMSARS is a validated, disease-specific scale representing the diverse signs and symptoms in MSA. Higher scores on the UMSARS scales mean poorer health.&#xD;
UMSARS has the following domains:&#xD;
Part I - Activities of Daily Living score (12 questions ranged in 0-4 [total score 0-48]) that evaluates motor including autonomic activities Part II - Motor Examination score (14 questions, [total score 0-56]) Part III - Autonomic Examination Part IV - Global disability scale ((1=completely independent; 2=not completely independent; 3=more dependent; 4=very dependent; 5=total dependent and helpless).&#xD;
Only UMSARS Part II total score is reported, which was obtained as the sum of the 14 items in the scale. If any of the items were missing, then the total score was considered missing. Higher scores indicate worse functional situation.</description>
        <time_frame>From baseline to week 12</time_frame>
        <population>The Per Protocol Population will include all randomized participants who do not have any entry criteria violations or protocol deviations that could significantly impact the assessment or interpretation of efficacy data.</population>
        <group_list>
          <group group_id="O1">
            <title>Safinamide</title>
            <description>Safinamide methanesulfonate film-coated tablets once daily. During the titration period of 2 weeks (Week 1 to Week 2) participants received 1 tablet (100 mg) safinamide, while during the treatment period (Week 3 to Week 12) they received 2 tablets (200 mg) safinamide once-a-day, taken in the morning, in addition to their daily levodopa dose.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Safinamide methanesulfonate matching placebo film-coated tablets once daily. Safinamide matching placebo was administered both during the titration period of 2 weeks (Week 1 to Week 2) and during the following period (Week 3 to Week 12), once daily, taken in the morning, in addition to their daily levodopa dose.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 12 in Unified Multiple System Atrophy Rating Scale (UMSARS), Part II (PP Population)</title>
          <description>UMSARS is a validated, disease-specific scale representing the diverse signs and symptoms in MSA. Higher scores on the UMSARS scales mean poorer health.&#xD;
UMSARS has the following domains:&#xD;
Part I - Activities of Daily Living score (12 questions ranged in 0-4 [total score 0-48]) that evaluates motor including autonomic activities Part II - Motor Examination score (14 questions, [total score 0-56]) Part III - Autonomic Examination Part IV - Global disability scale ((1=completely independent; 2=not completely independent; 3=more dependent; 4=very dependent; 5=total dependent and helpless).&#xD;
Only UMSARS Part II total score is reported, which was obtained as the sum of the 14 items in the scale. If any of the items were missing, then the total score was considered missing. Higher scores indicate worse functional situation.</description>
          <population>The Per Protocol Population will include all randomized participants who do not have any entry criteria violations or protocol deviations that could significantly impact the assessment or interpretation of efficacy data.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.1" spread="4.66"/>
                    <measurement group_id="O2" value="-0.6" spread="6.17"/>
                  </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>The model included treatment, week of visit, and treatment-by-visit interaction as fixed effects and baseline score as a covariate.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.5386</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>A mixed-model repeated measures (MMRM) was used to analyze the change in from baseline in UMSARS Part II.</method_desc>
            <param_type>least square mean difference</param_type>
            <param_value>-1.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.8</ci_lower_limit>
            <ci_upper_limit>2.6</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 12 in Multiple System Atrophy Health-Related Quality of Life (MSA-QoL) Scale</title>
        <description>The MSA-QoL is a self-reported questionnaire focusing on MSA-specific symptoms and has a scale ranging from 0 to 160, with 0= 'no problem' and 160= &quot;extreme problem&quot;.</description>
        <time_frame>From baseline to week 12</time_frame>
        <population>The ITT Population included all randomized participants. This population was used for all efficacy variables</population>
        <group_list>
          <group group_id="O1">
            <title>Safinamide</title>
            <description>Safinamide methanesulfonate film-coated tablets once daily. During the titration period of 2 weeks (Week 1 to Week 2) participants received 1 tablet (100 mg) safinamide, while during the treatment period (Week 3 to Week 12) they received 2 tablets (200 mg) safinamide once-a-day, taken in the morning, in addition to their daily levodopa dose.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Safinamide methanesulfonate matching placebo film-coated tablets once daily. Safinamide matching placebo was administered both during the titration period of 2 weeks (Week 1 to Week 2) and during the following period (Week 3 to Week 12), once daily, taken in the morning, in addition to their daily levodopa dose.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 12 in Multiple System Atrophy Health-Related Quality of Life (MSA-QoL) Scale</title>
          <description>The MSA-QoL is a self-reported questionnaire focusing on MSA-specific symptoms and has a scale ranging from 0 to 160, with 0= 'no problem' and 160= &quot;extreme problem&quot;.</description>
          <population>The ITT Population included all randomized participants. This population was used for all efficacy variables</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.6" spread="25.57"/>
                    <measurement group_id="O2" value="-2.9" spread="14.37"/>
                  </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>The model included treatment, week of visit, and treatment-by-visit interaction as fixed effects and baseline score as a covariate.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.3364</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>A mixed-model repeated measures (MMRM) was used to analyze the change in from baseline in MSA-QoL scale.</method_desc>
            <param_type>Least square mean difference</param_type>
            <param_value>6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-6.5</ci_lower_limit>
            <ci_upper_limit>18.6</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 12 in Montreal Cognitive Assessment (MoCA) Scale</title>
        <description>The Montreal Cognitive Assessment (MoCA) was designed as a tool for rapid screening for mild cognitive impairment. It evaluates different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructive skills, abstraction, calculation and orientation. The administration time of the MoCa is 10 minutes. The MoCA scale ranges from 0 to 30, with higher scores indicating better cognitive functioning.</description>
        <time_frame>From baseline to week 12</time_frame>
        <population>The ITT Population included all randomized participants. This population was used for all efficacy variables.</population>
        <group_list>
          <group group_id="O1">
            <title>Safinamide</title>
            <description>Safinamide methanesulfonate film-coated tablets once daily. During the titration period of 2 weeks (Week 1 to Week 2) participants received 1 tablet (100 mg) safinamide, while during the treatment period (Week 3 to Week 12) they received 2 tablets (200 mg) safinamide once-a-day, taken in the morning, in addition to their daily levodopa dose.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Safinamide methanesulfonate matching placebo film-coated tablets once daily. Safinamide matching placebo was administered both during the titration period of 2 weeks (Week 1 to Week 2) and during the following period (Week 3 to Week 12), once daily, taken in the morning, in addition to their daily levodopa dose.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 12 in Montreal Cognitive Assessment (MoCA) Scale</title>
          <description>The Montreal Cognitive Assessment (MoCA) was designed as a tool for rapid screening for mild cognitive impairment. It evaluates different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructive skills, abstraction, calculation and orientation. The administration time of the MoCa is 10 minutes. The MoCA scale ranges from 0 to 30, with higher scores indicating better cognitive functioning.</description>
          <population>The ITT Population included all randomized participants. This population was used for all efficacy variables.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="2.01"/>
                    <measurement group_id="O2" value="-0.3" spread="2.09"/>
                  </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>The ANCOVA included change from baseline as the response variable, treatment group as a factor, and baseline score as a covariate</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.7574</p_value>
            <method>ANCOVA</method>
            <param_type>Least square mean difference</param_type>
            <param_value>0.2</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.1</ci_lower_limit>
            <ci_upper_limit>1.5</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 12 in Unified Dystonia Rating Scale (UDRS)</title>
        <description>UDRS consists of a Historical Section, divided into questionnaires about 1) on-dyskinesia and 2) off -dystonia, and an Objective Section, divided into 3) impairment and 4) disability scales. The Historical Section is scored from 0-60, and the Objective section is scored 0-44, where higher scores reflect greater difficulty or impairment.&#xD;
The Unified Dystonia Rating Scale (UDRS) assesses the motor severity and duration of dystonia in 14 body areas. The total score, obtained as the sum of the severity and duration factors, ranges from 0 to 112. Higher scores indicate worse dystonia.</description>
        <time_frame>From baseline to week 12</time_frame>
        <population>The ITT Population included all randomized participants. This population was used for all efficacy variables.</population>
        <group_list>
          <group group_id="O1">
            <title>Safinamide</title>
            <description>Safinamide methanesulfonate film-coated tablets once daily. During the titration period of 2 weeks (Week 1 to Week 2) participants received 1 tablet (100 mg) safinamide, while during the treatment period (Week 3 to Week 12) they received 2 tablets (200 mg) safinamide once-a-day, taken in the morning, in addition to their daily levodopa dose.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Safinamide methanesulfonate matching placebo film-coated tablets once daily. Safinamide matching placebo was administered both during the titration period of 2 weeks (Week 1 to Week 2) and during the following period (Week 3 to Week 12), once daily, taken in the morning, in addition to their daily levodopa dose.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 12 in Unified Dystonia Rating Scale (UDRS)</title>
          <description>UDRS consists of a Historical Section, divided into questionnaires about 1) on-dyskinesia and 2) off -dystonia, and an Objective Section, divided into 3) impairment and 4) disability scales. The Historical Section is scored from 0-60, and the Objective section is scored 0-44, where higher scores reflect greater difficulty or impairment.&#xD;
The Unified Dystonia Rating Scale (UDRS) assesses the motor severity and duration of dystonia in 14 body areas. The total score, obtained as the sum of the severity and duration factors, ranges from 0 to 112. Higher scores indicate worse dystonia.</description>
          <population>The ITT Population included all randomized participants. This population was used for all efficacy variables.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" spread="4.82"/>
                    <measurement group_id="O2" value="0.3" spread="5.60"/>
                  </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>The model included treatment, week of visit, and treatment-by-visit interaction as fixed effects and baseline score as a covariate.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.6393</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>A mixed-model repeated measures (MMRM) was used to analyze the change from baseline in UDRS.</method_desc>
            <param_type>Least square mean difference</param_type>
            <param_value>0.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.5</ci_lower_limit>
            <ci_upper_limit>4.0</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>At baseline, at interim visits (Weeks 2 - 8, and more precisely at days 14 ± 3, 28 ± 3, 56 ± 3), at End of Treatment visit (EOT) at Week 12 (84 ± 3 days), and at follow-up call at week 14 ( 98 ± 3).</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Safinamide</title>
          <description>Safinamide methanesulfonate film-coated tablets once daily. During the titration period of 2 weeks (Week 1 to Week 2) participants received 1 tablet (100 mg) safinamide, while during the treatment period (Week 3 to Week 12) they received 2 tablets (200 mg) safinamide once-a-day, taken in the morning, in addition to their daily levodopa dose.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Safinamide methanesulfonate matching placebo film-coated tablets once daily. Safinamide matching placebo was administered both during the titration period of 2 weeks (Week 1 to Week 2) and during the following period (Week 3 to Week 12), once daily, taken in the morning, in addition to their daily levodopa dose.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA version 23.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="32"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac respiratory arrest</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA version 23.0</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="21" subjects_at_risk="32"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Conjunctival hyperaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Salivary hypersecretion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Peripheral swelling</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="32"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Escherichia infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Escherichia urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Oral fungal infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Pseudomonas infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="32"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Wound</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Chest injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Head injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Rib fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Tooth fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Increased appetite</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Bursitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Tendon disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Burning sensation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Dyskinesia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Nervous system disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Parkinsonian gait</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Parkinsonism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hallucination</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Nervousness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="32"/>
                <counts group_id="E2" events="4" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Dependent rubor</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="32"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Director of Clinical Trial - Charlotte Keywood, MD</name_or_title>
      <organization>Zambon S.p.A.</organization>
      <phone>+39 02 665241</phone>
      <email>charlotte.keywood@zambongroup.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/NCT03753763
org study id: Z7219K01
secondary id: 2018-004145-16
nct id: NCT03753763
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The study is a placebo controlled study, with two parallel arms, in which participants will
      be randomly assigned in a 2:1 ratio to receive either active (200 mg safinamide) or placebo
      in a double blind manner. Study population is patients diagnosed, with possible or probable
      parkinsonian variant of Multiple System Atrophy who are on a stable treatment of levodopa
The overall design is a parallel group, placebo controlled, double blind study. The target
      population are participants diagnosed with possible or probable parkinsonian variant of
      Multiple System Atrophy who are on stable doses of levodopa.

      Trial participation will be up to a maximum duration of 14 weeks and will comprise a
      screening period (up to 2 weeks), a 2-week run in period during which subjects will receive 1
      tablet (either 100 mg safinamide or matching placebo), followed by a 10-week period, during
      which study participants will take 2 tablets of study medication (200 mg safinamide or
      placebo) once daily, taken in the morning in addition to their morning levodopa dose. A
      telephone follow-up call will be performed 2 weeks after the end of treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: TEAEs (Treatment Emergent Adverse Events) and SAEs (Serious Adverse Events)
time frame: Throughout the study, from baseline (and at each interim visit) to telephone follow-up visit at 14 week.
description: While evaluating safety and tolerability of safinamide, 200 mg od, compared with placebo, severity of TEAEs, their relationship to study drug, their seriousness and their consequences were assessed. TEAEs were defined as adverse events (AEs) that started after the first dose of study drug.
measure: Change From Baseline to Week 12 in the Goniometric Measurement for Anterior Displacement
time frame: From baseline to week 12
description: To evaluate the potential efficacy of safinamide 200 mg od, as add-on therapy, on quality of life (change in anterior displacement). The goniometric measurement consists in the posture evaluation of the patient, measuring through a goniometer the angle of the flexion of the trunk. Goniometric measurement of "anterior" displacement was determined using a wall goniometer and expressing the value in degrees in the range of 0 to 90.
measure: Change From Baseline to Week 12 in the Goniometric Measurement for Lateral Displacement
time frame: From baseline to week 12
description: To evaluate the potential efficacy of safinamide 200 mg od, as add-on therapy, on quality of life (change in anterior displacement). The goniometric measurement consists in the posture evaluation of the patient, measuring through a goniometer the angle of the flexion of the trunk. Goniometric measurement of "lateral" displacement was determined using a wall goniometer and expressing the value in degrees in the range of 0 to 90.
measure: Change From Baseline to Week 12 in Unified Multiple System Atrophy Rating Scale (UMSARS), Part II (ITT Population)
time frame: From baseline to week 12
description: UMSARS is a validated, disease-specific scale representing the diverse signs and symptoms in MSA. Higher scores on the UMSARS scales mean poorer health.
UMSARS has the following domains:
Part I - Activities of Daily Living score (12 questions ranged in 0-4 [total score 0-48]) that evaluates motor including autonomic activities Part II - Motor Examination score (14 questions, [total score 0-56]) Part III - Autonomic Examination Part IV - Global disability scale ((1=completely independent; 2=not completely independent; 3=more dependent; 4=very dependent; 5=total dependent and helpless).
Only UMSARS Part II total score is reported, which was obtained as the sum of the 14 items in the scale. If any of the items were missing, then the total score was considered missing. Higher scores indicate worse functional situation.
measure: Change From Baseline to Week 12 in Unified Multiple System Atrophy Rating Scale (UMSARS), Part II (PP Population)
time frame: From baseline to week 12
description: UMSARS is a validated, disease-specific scale representing the diverse signs and symptoms in MSA. Higher scores on the UMSARS scales mean poorer health.
UMSARS has the following domains:
Part I - Activities of Daily Living score (12 questions ranged in 0-4 [total score 0-48]) that evaluates motor including autonomic activities Part II - Motor Examination score (14 questions, [total score 0-56]) Part III - Autonomic Examination Part IV - Global disability scale ((1=completely independent; 2=not completely independent; 3=more dependent; 4=very dependent; 5=total dependent and helpless).
Only UMSARS Part II total score is reported, which was obtained as the sum of the 14 items in the scale. If any of the items were missing, then the total score was considered missing. Higher scores indicate worse functional situation.
measure: Change From Baseline to Week 12 in Multiple System Atrophy Health-Related Quality of Life (MSA-QoL) Scale
time frame: From baseline to week 12
description: The MSA-QoL is a self-reported questionnaire focusing on MSA-specific symptoms and has a scale ranging from 0 to 160, with 0= 'no problem' and 160= "extreme problem".
measure: Change From Baseline to Week 12 in Montreal Cognitive Assessment (MoCA) Scale
time frame: From baseline to week 12
description: The Montreal Cognitive Assessment (MoCA) was designed as a tool for rapid screening for mild cognitive impairment. It evaluates different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructive skills, abstraction, calculation and orientation. The administration time of the MoCa is 10 minutes. The MoCA scale ranges from 0 to 30, with higher scores indicating better cognitive functioning.
measure: Change From Baseline to Week 12 in Unified Dystonia Rating Scale (UDRS)
time frame: From baseline to week 12
description: UDRS consists of a Historical Section, divided into questionnaires about 1) on-dyskinesia and 2) off -dystonia, and an Objective Section, divided into 3) impairment and 4) disability scales. The Historical Section is scored from 0-60, and the Objective section is scored 0-44, where higher scores reflect greater difficulty or impairment.
The Unified Dystonia Rating Scale (UDRS) assesses the motor severity and duration of dystonia in 14 body areas. The total score, obtained as the sum of the severity and duration factors, ranges from 0 to 112. Higher scores indicate worse dystonia.
arm group label: Active
arm group type: Experimental
description: Safinamide methanesulfonate film-coated tablets once daily
arm group label: Placebo
arm group type: Placebo Comparator
description: Safinamide Methanesulfonate matching placebo film-coated tablets once daily
intervention type: Drug
intervention name: Safinamide Methanesulfonate
description: 100 mg (free base)
arm group label: Active
other name: Xadago
intervention type: Drug
intervention name: Safinamide Methanesulfonate matching placebo
description: 100 mg placebo
arm group label: Placebo
other name: placebo
criteria: 
gender: All
minimum age: 30 Years
maximum age: 80 Years
healthy volunteers: No
last name: Charlotte Keywood, MD
role: Study Director
affiliation: Zambon SpA
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country: Italy
country: Spain
responsible party type: Sponsor
mesh term: Multiple System Atrophy
mesh term: Shy-Drager Syndrome
mesh term: Atrophy
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 