<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/NCT01705236</url>
  </required_header>
  <id_info>
    <org_study_id>CFTY720DDE15TS</org_study_id>
    <nct_id>NCT01705236</nct_id>
  </id_info>
  <brief_title>A 3-year Multi-center Study to Describe Changes of OCT Parameters Under Treatment With Gilenya®</brief_title>
  <acronym>PASSOS</acronym>
  <official_title>A 3-year Multi-center Study to Describe the Long Term Changes of Optical Coherence Tomography (OCT) Parameters in Patients Under Treatment With Gilenya®</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This was a 3-year, prospective, multi-center, open-label study to describe the long term&#xD;
      changes of optical coherence tomography (OCT) parameters in RRMS patients under treatment&#xD;
      with Fingolimod. It was designed to longitudinally study the degeneration of retinal axons by&#xD;
      measuring change in RNFL thickness by latest OCT-technology.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 20, 2012</start_date>
  <completion_date type="Actual">February 18, 2019</completion_date>
  <primary_completion_date type="Actual">February 18, 2019</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline to Month 36 in Average Retinal Nerve Fiber Layer Thickness (RNFLT)</measure>
    <time_frame>Baseline, month 36</time_frame>
    <description>The primary endpoint was the change, i.e. the absolute difference, in average RNFL thickness from baseline to month 36 (or last values in case of missing data) in the Full Analysis Set (FAS). Average RNFL thickness was the average of valid measurements of the right and left eye and assessed by optical coherence tomography (OCT).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Month 12 and 24 in Average Retinal Nerve Fiber Layer Thickness (RNFLT)</measure>
    <time_frame>Baseline, month 12, month 24</time_frame>
    <description>Change from baseline in average RNFL thickness to months 12 and 24 (or last values in case of missing data) in the Full Analysis Set (FAS). Average RNFL thickness was the average of valid measurements of the right and left eye and assessed by optical coherence tomography (OCT).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Month 12, 24 and 36 in Average Quadrant Retinal Nerve Fiber Layer Thickness (RNFLT)</measure>
    <time_frame>Baseline, month 12, month 24, month 36</time_frame>
    <description>Change from baseline in average quadrant RNFL thickness to months 12, 24 and 36 (or last values in case of missing data) in the Full Analysis Set (FAS). Average quadrant RNFL thickness was the average of valid measurements of the right and left eye and assessed by optical coherence tomography (OCT). Quadrant RNFL thickness were: Nasal-inferior; nasal-superior; temporal-inferior; temporal-superior.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Month 12, 24 and 36 in Total Macular Volume (TMV)</measure>
    <time_frame>12, 24 and 36 months</time_frame>
    <description>Change from baseline in TMV to months 12, 24 and 36 (or last values in case of missing data) in the Full Analysis Set (FAS).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Month 12, 24 and 36 in Ganglion Cell Inner Plexiform (GCIP)</measure>
    <time_frame>Baseline, month 12, month 24, month 36</time_frame>
    <description>Change from baseline in GCIP to months 12, 24 and 36 (or last values in case of missing data) in the Full Analysis Set (FAS).&#xD;
The change in Ganglion cell layer thickness (GCLT) had been defined as secondary endpoint in the protocol, but OCT measured the GCIP instead. This was done because both layers were not clearly separable by OCT. GCIP was calculated as mean of the inner sectors (nasal, superior, temporal, and inferior) and declared as usual parameter instead. This change was introduced prior to data base lock, but the derivation of GCIP was corrected after data base lock.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events</measure>
    <time_frame>36 months</time_frame>
    <description>Number of participants with adverse events and specifically macular edema.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">87</enrollment>
  <condition>Relapsing Remitting Multiple Sclerosis RRMS</condition>
  <arm_group>
    <arm_group_label>Fingolimod - Longitudinal Assessment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>No study drug was provided. Fingolimod was to be prescribed according to local label. The decision to prescribe fingolimod had to be made independent of this study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fingolimod</intervention_name>
    <description>All subjects received an oral dose of 0.5 mg fingolimod (FTY720) per capsule (hard gelatin capsules) once daily according to local label for the treatment of their MS.</description>
    <arm_group_label>Fingolimod - Longitudinal Assessment</arm_group_label>
    <other_name>FTY720</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
        Patients eligible for inclusion in this study have to fulfill all of the following&#xD;
        criteria:&#xD;
&#xD;
          1. Written informed consent must be obtained before any assessment is performed.&#xD;
&#xD;
          2. Male or female subjects aged 18-65 years.&#xD;
&#xD;
          3. Subjects with relapsing remitting MS defined by 2010 revised McDonald criteria (see&#xD;
             Appendix 4).&#xD;
&#xD;
          4. Patients with Expanded Disability Status Scale (EDSS) score of 0-6.0 inclusive (see&#xD;
             Appendix 6).&#xD;
&#xD;
          5. Patients stable on immunomodulatory treatment with fingolimod for at least 1 month and&#xD;
             at most 4 months prior to screening according to local label&#xD;
&#xD;
          6. Neurologically stable with no evidence of relapse within 30 days prior to inclusion&#xD;
             date&#xD;
&#xD;
          7. Sufficient ability to read, write, communicate and understand&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
        Patients fulfilling any of the following criteria are not eligible for inclusion in this&#xD;
        study:&#xD;
&#xD;
          1. Patients who have been treated with:&#xD;
&#xD;
               -  systemic corticosteroids or immunoglobulins within 1 month prior to screening;&#xD;
&#xD;
               -  immunosuppressive medications such as azathioprine, cyclophosphamide, or&#xD;
                  methotrexate within 3 months prior to screening;&#xD;
&#xD;
               -  monoclonal antibodies (including natalizumab) within 3 months prior to screening;&#xD;
&#xD;
               -  mitoxantrone within 6 months prior to screening&#xD;
&#xD;
               -  cladribine at any time.&#xD;
&#xD;
          2. Patients with any medically unstable condition, as assessed by the primary treating&#xD;
             physician at each site.&#xD;
&#xD;
          3. Patients with any of the following cardiovascular conditions :&#xD;
&#xD;
               -  history of myocardial infarction or with current unstable ischemic heart disease;&#xD;
&#xD;
               -  Heart failure (NYHA III-IV) or any severe cardiac disease as determined by the&#xD;
                  Investigator (see Appendix 5);&#xD;
&#xD;
               -  history or presence of a second-degree AV block, Type II or a third-degree AV&#xD;
                  block&#xD;
&#xD;
               -  patients receiving Class Ia (ajmaline, disopyramide, procainamide, quinidine) or&#xD;
                  III antiarrhythmic drugs (e.g., amiodarone, bretylium, sotalol, ibulitide,&#xD;
                  azimilide, dofelitide);&#xD;
&#xD;
               -  proven history of sick sinus syndrome;&#xD;
&#xD;
               -  uncontrolled hypertension&#xD;
&#xD;
          4. Patients with severe respiratory disease, pulmonary fibrosis, or chronic obstructive&#xD;
             pulmonary disease (Class III-IV).&#xD;
&#xD;
          5. Patients with history of specific MRI findings (tumor, subdural haematoma,&#xD;
             post-contusional changes, territorial stroke, neurodegenerative disorders,&#xD;
             aneurysm/arteriovenous malformation, evidence of past macroscopic haemorrhage, or&#xD;
             other relevant MRI findings that would interfere with evaluation)&#xD;
&#xD;
          6. Any severe disability or clinical impairment that can prevent the patient to meet all&#xD;
             study requirements at the investigator's discretion&#xD;
&#xD;
          7. History of malignancy of any organ system, treated or untreated, within the past 5&#xD;
             years whether or not there is evidence of local recurrence or metastases, with the&#xD;
             exception of localized basal cell carcinoma of the skin&#xD;
&#xD;
          8. Patients who have received an investigational drug (excluding fingolimod) or therapy&#xD;
             within 90 days or 5 half-lives of screening, whichever is longer.&#xD;
&#xD;
          9. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a&#xD;
             female after conception and until the termination of gestation, confirmed by a&#xD;
             positive hCG test (serum)&#xD;
&#xD;
         10. Patients with any ophthalmologic reason for RNFL pathology other than MS, such as:&#xD;
             optic neuropathy, active advanced glaucoma, injury of the optic nerve based on the&#xD;
             ophthalmologist's clinical judgment&#xD;
&#xD;
         11. history or presence of severe myopia&#xD;
&#xD;
               1. in patients who have not had refractive surgery, a refractive error of greater&#xD;
                  than 6.00 diopters&#xD;
&#xD;
               2. pathologic fundus changes of high myopia, such as retinal pigmentary atrophy,&#xD;
                  besides peripapillary atrophy (atrophy involving the macula) or a staphyloma&#xD;
&#xD;
               3. in patients that have had previous refractive surgery, an axial eye length of&#xD;
                  greater than 26 mm&#xD;
&#xD;
         12. Acute optic neuritis within the past 6 months before screening&#xD;
&#xD;
         13. Evidence of advanced, non-proliferative or proliferative diabetic retinopathy&#xD;
&#xD;
         14. Presence of retinal conditions associated with edema, subretinal fluid, cysts, etc.&#xD;
&#xD;
         15. Concomitant use of drugs that may directly affect retinal structure and function (e.g.&#xD;
&#xD;
        chronic systemic corticosteroids [&gt;30 consecutive days; doses higher than Cushing threshold&#xD;
        e.g. prednisone 7.5mg/d], intraocular anti-angiogenic drugs [ranibizumab, bevacizumab],&#xD;
        intraocular steroids etc.)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bochum</city>
        <zip>44791</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bonn</city>
        <zip>53105</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Dresden</city>
        <zip>01307</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Duesseldorf</city>
        <zip>40225</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hannover</city>
        <zip>30625</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Heidelberg</city>
        <zip>69120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Leipzig</city>
        <zip>04103</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Rostock</city>
        <zip>18057</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ulm</city>
        <zip>89081</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Zuerich</city>
        <zip>8091</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>August 13, 2012</study_first_submitted>
  <study_first_submitted_qc>October 11, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 12, 2012</study_first_posted>
  <results_first_submitted>February 14, 2020</results_first_submitted>
  <results_first_submitted_qc>February 14, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">March 2, 2020</results_first_posted>
  <last_update_submitted>February 14, 2020</last_update_submitted>
  <last_update_submitted_qc>February 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 2, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Multiple sclerosis (MS)</keyword>
  <keyword>MS</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Multiple Sclerosis, Relapsing-Remitting</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fingolimod Hydrochloride</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.</ipd_description>
  </patient_data>
  <provided_document_section>
    <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>March 26, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/36/NCT01705236/SAP_000.pdf</document_url>
    </provided_document>
    <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 26, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/36/NCT01705236/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Subjects were screened at 10 study centers in Germany (9 centers) and Switzerland (1 center).</recruitment_details>
      <pre_assignment_details>Subjects who passed the screening were enrolled in the trial.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Fingolimod - Longitudinal Assessment</title>
          <description>No study drug was provided. Fingolimod was to be prescribed according to local label. The decision to prescribe fingolimod was to be made independent of this study.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="87"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="60"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Administrative problems</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Unsatisfactory therapeutic effect</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Abnormal test procedure result(s)</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Abnormal laboratory value(s)</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Fingolimod - Longitudinal Assessment</title>
          <description>No study drug was provided. Fingolimod was to be prescribed according to local label. The decision to prescribe fingolimod was to be made independent of this study.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="87"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="35.9" spread="9.5"/>
                  </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="55"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Caucasian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="84"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline to Month 36 in Average Retinal Nerve Fiber Layer Thickness (RNFLT)</title>
        <description>The primary endpoint was the change, i.e. the absolute difference, in average RNFL thickness from baseline to month 36 (or last values in case of missing data) in the Full Analysis Set (FAS). Average RNFL thickness was the average of valid measurements of the right and left eye and assessed by optical coherence tomography (OCT).</description>
        <time_frame>Baseline, month 36</time_frame>
        <population>Full Analysis Set (FAS). The FAS consisted of all subjects treated with fingolimod who had at least one post-baseline efficacy assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Fingolimod - Longitudinal Assessment</title>
            <description>No study drug was provided. Fingolimod was to be prescribed according to local label. The decision to prescribe fingolimod was to be made independent of this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Month 36 in Average Retinal Nerve Fiber Layer Thickness (RNFLT)</title>
          <description>The primary endpoint was the change, i.e. the absolute difference, in average RNFL thickness from baseline to month 36 (or last values in case of missing data) in the Full Analysis Set (FAS). Average RNFL thickness was the average of valid measurements of the right and left eye and assessed by optical coherence tomography (OCT).</description>
          <population>Full Analysis Set (FAS). The FAS consisted of all subjects treated with fingolimod who had at least one post-baseline efficacy assessment.</population>
          <units>micrometer</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="72"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.5" spread="2.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Month 12 and 24 in Average Retinal Nerve Fiber Layer Thickness (RNFLT)</title>
        <description>Change from baseline in average RNFL thickness to months 12 and 24 (or last values in case of missing data) in the Full Analysis Set (FAS). Average RNFL thickness was the average of valid measurements of the right and left eye and assessed by optical coherence tomography (OCT).</description>
        <time_frame>Baseline, month 12, month 24</time_frame>
        <population>Full Analysis Set (FAS). The FAS consisted of all subjects treated with fingolimod who had at least one post-baseline efficacy assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Fingolimod - Longitudinal Assessment</title>
            <description>No study drug was provided. Fingolimod was to be prescribed according to local label. The decision to prescribe fingolimod was to be made independent of this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Month 12 and 24 in Average Retinal Nerve Fiber Layer Thickness (RNFLT)</title>
          <description>Change from baseline in average RNFL thickness to months 12 and 24 (or last values in case of missing data) in the Full Analysis Set (FAS). Average RNFL thickness was the average of valid measurements of the right and left eye and assessed by optical coherence tomography (OCT).</description>
          <population>Full Analysis Set (FAS). The FAS consisted of all subjects treated with fingolimod who had at least one post-baseline efficacy assessment.</population>
          <units>micrometer</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="72"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from baseline to month 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.8" spread="2.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline to month 24</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.1" spread="2.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Month 12, 24 and 36 in Average Quadrant Retinal Nerve Fiber Layer Thickness (RNFLT)</title>
        <description>Change from baseline in average quadrant RNFL thickness to months 12, 24 and 36 (or last values in case of missing data) in the Full Analysis Set (FAS). Average quadrant RNFL thickness was the average of valid measurements of the right and left eye and assessed by optical coherence tomography (OCT). Quadrant RNFL thickness were: Nasal-inferior; nasal-superior; temporal-inferior; temporal-superior.</description>
        <time_frame>Baseline, month 12, month 24, month 36</time_frame>
        <population>Full Analysis Set (FAS). The FAS consisted of all subjects treated with fingolimod who had at least one post-baseline efficacy assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Fingolimod - Longitudinal Assessment</title>
            <description>No study drug was provided. Fingolimod was to be prescribed according to local label. The decision to prescribe fingolimod was to be made independent of this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Month 12, 24 and 36 in Average Quadrant Retinal Nerve Fiber Layer Thickness (RNFLT)</title>
          <description>Change from baseline in average quadrant RNFL thickness to months 12, 24 and 36 (or last values in case of missing data) in the Full Analysis Set (FAS). Average quadrant RNFL thickness was the average of valid measurements of the right and left eye and assessed by optical coherence tomography (OCT). Quadrant RNFL thickness were: Nasal-inferior; nasal-superior; temporal-inferior; temporal-superior.</description>
          <population>Full Analysis Set (FAS). The FAS consisted of all subjects treated with fingolimod who had at least one post-baseline efficacy assessment.</population>
          <units>micrometer</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="72"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Nasal-superior RNFL thickness: month 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5" spread="4.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nasal-superior RNFL thickness: month 24</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.4" spread="3.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nasal-superior RNFL thickness: month 36</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.7" spread="3.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nasal-inferior RNFL thickness: month 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.2" spread="4.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nasal-inferior RNFL thickness: month 24</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.6" spread="5.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nasal-inferior RNFL thickness: month 36</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.1" spread="5.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Temporal-inferior RNFL thickness: month 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.2" spread="2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Temporal-inferior RNFL thickness: month 24</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.6" spread="3.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Temporal-inferior RNFL thickness: month 36</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.3" spread="4.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Temporal-superior RNFL thickness: month 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5" spread="3.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Temporal-superior RNFL thickness: month 24</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.4" spread="3.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Temporal-superior RNFL thickness: month 36</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.1" spread="4.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Month 12, 24 and 36 in Total Macular Volume (TMV)</title>
        <description>Change from baseline in TMV to months 12, 24 and 36 (or last values in case of missing data) in the Full Analysis Set (FAS).</description>
        <time_frame>12, 24 and 36 months</time_frame>
        <population>Full Analysis Set (FAS). The FAS consisted of all subjects treated with fingolimod who had at least one post-baseline efficacy assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Fingolimod - Longitudinal Assessment</title>
            <description>No study drug was provided. Fingolimod was to be prescribed according to local label. The decision to prescribe fingolimod was to be made independent of this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Month 12, 24 and 36 in Total Macular Volume (TMV)</title>
          <description>Change from baseline in TMV to months 12, 24 and 36 (or last values in case of missing data) in the Full Analysis Set (FAS).</description>
          <population>Full Analysis Set (FAS). The FAS consisted of all subjects treated with fingolimod who had at least one post-baseline efficacy assessment.</population>
          <units>Cubic millimeter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="72"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from baseline to month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="71"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.03" spread="0.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline to month 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="71"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.04" spread="0.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline to month 36</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="71"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.06" spread="0.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Month 12, 24 and 36 in Ganglion Cell Inner Plexiform (GCIP)</title>
        <description>Change from baseline in GCIP to months 12, 24 and 36 (or last values in case of missing data) in the Full Analysis Set (FAS).&#xD;
The change in Ganglion cell layer thickness (GCLT) had been defined as secondary endpoint in the protocol, but OCT measured the GCIP instead. This was done because both layers were not clearly separable by OCT. GCIP was calculated as mean of the inner sectors (nasal, superior, temporal, and inferior) and declared as usual parameter instead. This change was introduced prior to data base lock, but the derivation of GCIP was corrected after data base lock.</description>
        <time_frame>Baseline, month 12, month 24, month 36</time_frame>
        <population>Full Analysis Set (FAS). The FAS consisted of all subjects treated with fingolimod who had at least one post-baseline efficacy assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Fingolimod - Longitudinal Assessment</title>
            <description>No study drug was provided. Fingolimod was to be prescribed according to local label. The decision to prescribe fingolimod was to be made independent of this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Month 12, 24 and 36 in Ganglion Cell Inner Plexiform (GCIP)</title>
          <description>Change from baseline in GCIP to months 12, 24 and 36 (or last values in case of missing data) in the Full Analysis Set (FAS).&#xD;
The change in Ganglion cell layer thickness (GCLT) had been defined as secondary endpoint in the protocol, but OCT measured the GCIP instead. This was done because both layers were not clearly separable by OCT. GCIP was calculated as mean of the inner sectors (nasal, superior, temporal, and inferior) and declared as usual parameter instead. This change was introduced prior to data base lock, but the derivation of GCIP was corrected after data base lock.</description>
          <population>Full Analysis Set (FAS). The FAS consisted of all subjects treated with fingolimod who had at least one post-baseline efficacy assessment.</population>
          <units>micrometer</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="72"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from baseline to month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="71"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.49" spread="2.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline to month 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="71"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.42" spread="2.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline to month 36</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="71"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.46" spread="3.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events</title>
        <description>Number of participants with adverse events and specifically macular edema.</description>
        <time_frame>36 months</time_frame>
        <population>Safety Population (SAF). The SAF consisted of all subjects treated with fingolimod for whom safety information had been collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Fingolimod - Longitudinal Assessment</title>
            <description>No study drug was provided. Fingolimod was to be prescribed according to local label. The decision to prescribe fingolimod was to be made independent of this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events</title>
          <description>Number of participants with adverse events and specifically macular edema.</description>
          <population>Safety Population (SAF). The SAF consisted of all subjects treated with fingolimod for whom safety information had been collected.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="87"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>No. of subjects with any AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No. of subjects with macular edema</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Fingolimod - Longitudinal Assessment</title>
          <description>No study drug was provided. Fingolimod was to be prescribed according to local label. The decision to prescribe fingolimod was to be made independent of this study.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (21.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="87"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="87"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>AORTIC VALVE INCOMPETENCE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="87"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>ERYSIPELAS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="87"/>
              </event>
              <event>
                <sub_title>GASTROENTERITIS VIRAL</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="87"/>
              </event>
              <event>
                <sub_title>OPHTHALMIC HERPES ZOSTER</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="87"/>
              </event>
              <event>
                <sub_title>WOUND INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="87"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>LOWER LIMB FRACTURE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="87"/>
              </event>
              <event>
                <sub_title>RADIUS FRACTURE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="87"/>
              </event>
              <event>
                <sub_title>SUTURE RELATED COMPLICATION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="87"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>INTERVERTEBRAL DISC PROTRUSION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="87"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>CERVIX CARCINOMA STAGE 0</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="87"/>
              </event>
              <event>
                <sub_title>NASAL NEOPLASM</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="87"/>
              </event>
              <event>
                <sub_title>UTERINE LEIOMYOMA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="87"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>MULTIPLE SCLEROSIS RELAPSE</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="87"/>
              </event>
              <event>
                <sub_title>NEURALGIC AMYOTROPHY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="87"/>
              </event>
              <event>
                <sub_title>UHTHOFF'S PHENOMENON</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="87"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>CERVICAL DYSPLASIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="87"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (21.0)</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="68" subjects_at_risk="87"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>LYMPHOPENIA</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="87"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>DIARRHOEA</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="87"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>BRONCHITIS</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="87"/>
              </event>
              <event>
                <sub_title>CONJUNCTIVITIS</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="87"/>
              </event>
              <event>
                <sub_title>NASOPHARYNGITIS</sub_title>
                <counts group_id="E1" subjects_affected="41" subjects_at_risk="87"/>
              </event>
              <event>
                <sub_title>SINUSITIS</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="87"/>
              </event>
              <event>
                <sub_title>UPPER RESPIRATORY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="87"/>
              </event>
              <event>
                <sub_title>URINARY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="87"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>VITAMIN D DEFICIENCY</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="87"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>ARTHRALGIA</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="87"/>
              </event>
              <event>
                <sub_title>BACK PAIN</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="87"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>DIZZINESS</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="87"/>
              </event>
              <event>
                <sub_title>HEADACHE</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="87"/>
              </event>
              <event>
                <sub_title>MULTIPLE SCLEROSIS RELAPSE</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="87"/>
              </event>
              <event>
                <sub_title>PARAESTHESIA</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="87"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>DEPRESSION</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="87"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>COUGH</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="87"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>ALOPECIA</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="87"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>HYPERTENSION</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="87"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Novartis Pharmaceuticals</organization>
      <phone>862-778-8300</phone>
      <email>Novartis.email@novartis.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/NCT01705236
org study id: CFTY720DDE15TS
nct id: NCT01705236
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This was a 3-year, prospective, multi-center, open-label study to describe the long term
      changes of optical coherence tomography (OCT) parameters in RRMS patients under treatment
      with Fingolimod. It was designed to longitudinally study the degeneration of retinal axons by
      measuring change in RNFL thickness by latest OCT-technology.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Change From Baseline to Month 36 in Average Retinal Nerve Fiber Layer Thickness (RNFLT)
time frame: Baseline, month 36
description: The primary endpoint was the change, i.e. the absolute difference, in average RNFL thickness from baseline to month 36 (or last values in case of missing data) in the Full Analysis Set (FAS). Average RNFL thickness was the average of valid measurements of the right and left eye and assessed by optical coherence tomography (OCT).
measure: Change From Baseline to Month 12 and 24 in Average Retinal Nerve Fiber Layer Thickness (RNFLT)
time frame: Baseline, month 12, month 24
description: Change from baseline in average RNFL thickness to months 12 and 24 (or last values in case of missing data) in the Full Analysis Set (FAS). Average RNFL thickness was the average of valid measurements of the right and left eye and assessed by optical coherence tomography (OCT).
measure: Change From Baseline to Month 12, 24 and 36 in Average Quadrant Retinal Nerve Fiber Layer Thickness (RNFLT)
time frame: Baseline, month 12, month 24, month 36
description: Change from baseline in average quadrant RNFL thickness to months 12, 24 and 36 (or last values in case of missing data) in the Full Analysis Set (FAS). Average quadrant RNFL thickness was the average of valid measurements of the right and left eye and assessed by optical coherence tomography (OCT). Quadrant RNFL thickness were: Nasal-inferior; nasal-superior; temporal-inferior; temporal-superior.
measure: Change From Baseline to Month 12, 24 and 36 in Total Macular Volume (TMV)
time frame: 12, 24 and 36 months
description: Change from baseline in TMV to months 12, 24 and 36 (or last values in case of missing data) in the Full Analysis Set (FAS).
measure: Change From Baseline to Month 12, 24 and 36 in Ganglion Cell Inner Plexiform (GCIP)
time frame: Baseline, month 12, month 24, month 36
description: Change from baseline in GCIP to months 12, 24 and 36 (or last values in case of missing data) in the Full Analysis Set (FAS).
The change in Ganglion cell layer thickness (GCLT) had been defined as secondary endpoint in the protocol, but OCT measured the GCIP instead. This was done because both layers were not clearly separable by OCT. GCIP was calculated as mean of the inner sectors (nasal, superior, temporal, and inferior) and declared as usual parameter instead. This change was introduced prior to data base lock, but the derivation of GCIP was corrected after data base lock.
measure: Number of Participants With Adverse Events
time frame: 36 months
description: Number of participants with adverse events and specifically macular edema.
arm group label: Fingolimod - Longitudinal Assessment
arm group type: Experimental
description: No study drug was provided. Fingolimod was to be prescribed according to local label. The decision to prescribe fingolimod had to be made independent of this study.
intervention type: Drug
intervention name: Fingolimod
description: All subjects received an oral dose of 0.5 mg fingolimod (FTY720) per capsule (hard gelatin capsules) once daily according to local label for the treatment of their MS.
arm group label: Fingolimod - Longitudinal Assessment
other name: FTY720
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
country: Switzerland
responsible party type: Sponsor
mesh term: Multiple Sclerosis
mesh term: Multiple Sclerosis, Relapsing-Remitting
mesh term: Sclerosis
mesh term: Fingolimod Hydrochloride
sharing ipd: Undecided
ipd description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 