<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/NCT03773796</url>
  </required_header>
  <id_info>
    <org_study_id>1.3</org_study_id>
    <nct_id>NCT03773796</nct_id>
  </id_info>
  <brief_title>Nabilone for Non-motor Symptoms in Parkinson's Disease</brief_title>
  <acronym>NMS-Nab2</acronym>
  <official_title>Nabilone for Non-motor Symptoms in Parkinson's Disease: An Open-label Study to Evaluate Long-term Safety and Efficacy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University Innsbruck</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University Innsbruck</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label extension study for participants of the randomized placebo-controlled,&#xD;
      double-blind, parallel-group, enriched enrolment randomized withdrawal NMS-Nab Study,&#xD;
      assessing the long-term safety and efficacy of nabilone for non-motor symptoms in patients&#xD;
      with Parkinson´s Disease (PD). Nabilone is an analogue of tetrahydrocannabinol (THC), the&#xD;
      psychoactive component of cannabis. Nabilone acts as a partial agonist on both Cannabinoid 1&#xD;
      (CB1) and Cannabinoid 2 (CB2) receptor in humans and therefore mimics the effect of THC but&#xD;
      with more predictable side effects and less euphoria.&#xD;
&#xD;
      Eligible patients will be re-tapered in an open-label nabilone dose optimization phase&#xD;
      followed by an open-label period of 6 months on a stable nabilone dose.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label extension study for participants of the randomized placebo-controlled,&#xD;
      double-blind, parallel-group, enriched enrolment randomized withdrawal NMS-Nab Study,&#xD;
      assessing the long-term safety and efficacy of nabilone for non-motor symptoms in patients&#xD;
      with Parkinson´s Disease. Nabilone is an analogue of tetrahydrocannabinol (THC), the&#xD;
      psychoactive component of cannabis.&#xD;
&#xD;
      Eligible subjects will be re-tapered with open-label nabilone, optimally up to the dose the&#xD;
      patient had in the NMS-Nab Trial. It is the investigator´s decision to modify this dose, if&#xD;
      necessary. The re-tapering will be performed up to a maximum dose of 1 mg twice daily.&#xD;
      Treatment responders will enter the open-label treatment period for 6 months with visits&#xD;
      being performed every 3 months in the context of the patient´s regularly scheduled visits in&#xD;
      the specialized outpatient department. The last visit will be the Termination Visit.&#xD;
      Following this, nabilone will be tapered. During this period the patients will receive phone&#xD;
      calls every other day. A Safety Follow-Up Visit will be performed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 6, 2018</start_date>
  <completion_date type="Actual">January 31, 2020</completion_date>
  <primary_completion_date type="Actual">January 31, 2020</primary_completion_date>
  <phase>Phase 3</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>
    <intervention_model_description>open-label</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>None, open-label</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>AEs in PD Patients Taking Nabilone, Between V 1 and V 3</measure>
    <time_frame>6 months</time_frame>
    <description>Safety and tolerability will be evaluated with reference to the following:&#xD;
Adverse Events (AE)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Subjects (%) Who Discontinue the Study Due to an AE Between V 1 and V 3</measure>
    <time_frame>6 months</time_frame>
    <description>Safety and tolerability will be evaluated with reference to the following:&#xD;
Number of subjects (%) who discontinue the study due to an AE The reasons for discontinuation will be grouped in &quot;discontinuation due to an AE&quot; and &quot;discontinuation due to other reasons&quot;. Both results will be provided separately.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Subjects (%) Who Discontinue the Study Due to Other Reasons Than an AE Between V 1 and V 3</measure>
    <time_frame>6 months</time_frame>
    <description>Safety and tolerability will be evaluated with reference to the following:&#xD;
Number of subjects (%) who discontinue the study due to other reasons than an AE The reasons for discontinuation will be grouped in &quot;discontinuation due to an AE&quot; and &quot;discontinuation due to other reasons&quot;. Both results will be provided separately.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Suicidality in PD Patients Taking Nabilone Between V 1 and V 3 Using the Columbia-Suicide Severity Rating Scale</measure>
    <time_frame>between V 1 and V 3 (6 months)</time_frame>
    <description>Change in aggregated data of the Columbia-Suicide Severity Rating Scale (C-SSRS).&#xD;
Different questions for suicidality with the possible answers yes or no. Yes represents a worse outcome. Count of participants with new suicidality is given.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hallucinations in PD Patients Taking Nabilone Between V 1 and V 3</measure>
    <time_frame>between V 1 and V 3 (6 months)</time_frame>
    <description>Changes in points of the:&#xD;
Hallucination item (1.2) of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) Each item has a minimum of 0 and a maximum of 4 points with higher score values representing a worse outcome.&#xD;
Participant count with a change in the hallucination item is reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Day-time Sleepiness in PD Patients Taking Nabilone Between V 1 and V 3</measure>
    <time_frame>between V 1 and V 3 (6 months)</time_frame>
    <description>Changes in points of the:&#xD;
Day-time sleepiness item (1.8) of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) Each item has a minimum of 0 and a maximum of 4 points with higher score values representing a worse outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Orthostatic Hypotension in PD Patients Taking Nabilone Between V 1 and V 3</measure>
    <time_frame>between V 1 and V 3 (6 months)</time_frame>
    <description>Changes in points of the:&#xD;
Orthostatic hypotension item (1.12) of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS)&#xD;
Each item has a minimum of 0 and a maximum of 4 points with higher score values representing a worse outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Subject Compliance in PD Patients Taking Nabilone.</measure>
    <time_frame>between V 1 and V 3 (6 months)</time_frame>
    <description>subject incompliance as per drug accountability (%)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in Supine and Standing Blood Pressure Measurements (mmHg) in PD Patients Taking Nabilone Between V 1 and V 3</measure>
    <time_frame>between V 1 and V 3 (6 months)</time_frame>
    <description>changes in supine and standing blood pressure measurements (mmHg)&#xD;
Row titles:&#xD;
Mean Change of systolic blood pressure readings (SBP) from supine to standing position for 3 min at V 1&#xD;
Mean Change of systolic blood pressure readings (SBP) from supine to standing position for 3 min at V 3&#xD;
Mean Change of diastolic blood pressure readings (DBP) from supine to standing position for 3 min at V 1&#xD;
Mean Change of diastolic blood pressure readings (DBP) from supine to standing position for 3 min at V 3</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in Motor and Non-motor Symptoms in Patients With PD Taking Nabilone Between V 1 and V 3</measure>
    <time_frame>between V 1 and V 3 (6 months)</time_frame>
    <description>Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:&#xD;
Total and different parts of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) Part I: minimum points: 0, maximum points: 52, higher score values indicate a worse outcome.&#xD;
Part II: minimum points: 0, maximum points: 52, higher score values indicate a worse outcome.&#xD;
Part III: minimum points: 0, maximum points: 132, higher score values indicate a worse outcome.&#xD;
Part IV: minimum points: 0, maximum points: 24, higher score values indicate a worse outcome.&#xD;
Total Score: minimum points: 0, maximum points: 272, higher score values indicate a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Non-motor Symptoms (NMSS) in Patients With PD Taking Nabilone Between V 1 and V 3</measure>
    <time_frame>between V 1 and V 3 (6 months)</time_frame>
    <description>Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:&#xD;
Non Motor Symptoms Scale (NMSS) Minimum: 0, maximum: 360, higher score values indicate a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Non-motor Symptoms (HADS) in Patients With PD Taking Nabilone Between V 1 and V 3</measure>
    <time_frame>between V 1 and V 3 (6 months)</time_frame>
    <description>Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:&#xD;
Hospital anxiety and depression scale (HADS), HADS-A assesses anxiety, HADS-D depression.&#xD;
Total scale: minimum: 0, maximum: 42, separate HADS-A/-D score: minimum: 0, maximum: 21.&#xD;
Higher score values indicate a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Quality of Life in Patients With PD Taking Nabilone Between V 1 and V 3</measure>
    <time_frame>between V 1 and V 3 (6 months)</time_frame>
    <description>Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:&#xD;
Parkinson´s Disease Questionnaire - 8 (PDQ-8). Minimum: 0, maximum: 42, higher score values indicate a worse outcome.&#xD;
PDQ-8 was standardized, therefore the score ranges from 0 to 100 (= PDQ-8 Summary Index).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Sleepiness in Patients With PD Taking Nabilone Between V 1 and V 3</measure>
    <time_frame>between V 1 and V 3 (6 months)</time_frame>
    <description>Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:&#xD;
Epworth Sleepiness Scale (ESS) Minimum: 0, maximum: 24, higher score values indicate a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Fatigue in Patients With PD Taking Nabilone Between V 1 and V 3</measure>
    <time_frame>between V 1 and V 3 (6 months)</time_frame>
    <description>Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:&#xD;
Fatigue Severity Scale (FSS). Minimum: 9, maximum: 63, higher score values indicate a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Pain in Patients With PD Taking Nabilone Between V 1 and V 3</measure>
    <time_frame>between V 1 and V 3 (6 months)</time_frame>
    <description>Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:&#xD;
King's Parkinson's disease pain scale (KPPS) Minimum: 0, maximum: 168, higher score values indicate a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Impulsive-compulsive Behaviour in Patients With PD Taking Nabilone Between V 1 and V 3</measure>
    <time_frame>between V 1 and V 3 (6 months)</time_frame>
    <description>Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:&#xD;
Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) Minimum: 0, maximum: 112, higher score values indicate a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Overall Symptoms in Patients With PD Taking Nabilone Between V 1 and V 3</measure>
    <time_frame>between V 1 and V 3 (6 months)</time_frame>
    <description>Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:&#xD;
Clinical Global Impression - Global Improvement (CGI-I) Minimum: 1, maximum: 7, higher score values indicate a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Cognitive Function (MoCA) in Patients With PD Taking Nabilone Between V 1 and V 3</measure>
    <time_frame>from Screening of the preceding study (NCT03769896) to V 3 of this study (a maximum of 2 years, at study completion)</time_frame>
    <description>The change of Montreal Cognitive Assessment (MoCA, minimum 0 points, maximum 30 points, higher score values indicate better outcome) score values between the Screening Visit of the NMS-Nab Study (before the first intake of nabilone medication) and the termination visit of this study will be assessed as secondary efficacy endpoints.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Cognitive Function (MMSE) in Patients With PD Taking Nabilone</measure>
    <time_frame>from screening of the preceding study (NCT03769896) to V 3 of this study (a maximum of 2 years, at study completion)</time_frame>
    <description>The change of Mini Mental State Exam (MMSE, minimum 0 points, maximum 30 points, higher score values indicate better outcome) between the Screening Visit of the NMS-Nab Study (before the first intake of nabilone medication) and the termination visit of this study will be assessed as secondary efficacy endpoints.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Eye-tracking Evaluation in PD Patients Taking Nabilone at Visit V 2 to Assess Changes in Reaction Time.</measure>
    <time_frame>a maximum of 2 years, measurement at V2 visit</time_frame>
    <description>Change of the reaction time (seconds), between Screening and Termination Visit of the randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study and V 2 of this study as measured by the Eye-tracking examination.</description>
  </other_outcome>
  <other_outcome>
    <measure>Eye-tracking Evaluation in PD Patients Taking Nabilone at Visit V 2 to Assess Changes in Attention Span.</measure>
    <time_frame>a maximum of 2 years, measurement at V2 visit</time_frame>
    <description>Change of attention span (error rate, correct trials) between Screening and Termination Visit of the randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study and V 2 of this study as measured by the Eye-tracking examination.</description>
  </other_outcome>
  <other_outcome>
    <measure>Eye-tracking Evaluation in PD Patients Taking Nabilone at Visit V 2 to Assess Changes in the Ability to Concentrate.</measure>
    <time_frame>a maximum of 2 years, measurement at V2 visit</time_frame>
    <description>Change of ability to concentrate (error rate, correct trials) between Screening and Termination Visit of the randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study and V 2 of this study as measured by the Eye-tracking examination.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">22</enrollment>
  <condition>Parkinson Disease</condition>
  <arm_group>
    <arm_group_label>Treatment Group</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nabilone 0.25 mg</intervention_name>
    <description>capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis</description>
    <arm_group_label>Treatment Group</arm_group_label>
    <other_name>Canemes</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        In order to be eligible for participation in the study, subjects must meet all inclusion&#xD;
        criteria:&#xD;
&#xD;
          1. In order to be eligible for the study, patients must have completed the double-blind&#xD;
             phase of the NMS-Nab trial as responders within the last 2 months.&#xD;
&#xD;
          2. For patients that completed NMS-Nab Study over 2 months prior to the Screening /&#xD;
             Baseline Visit, and meet all other inclusion criteria, eligibility should be discussed&#xD;
             on a case-by-case basis.&#xD;
&#xD;
          3. Only patients without a drug-related serious adverse event (SAE) or (drug-related)&#xD;
             moderate or severe AE during the NMS-Nab Study can be included in the study&#xD;
&#xD;
          4. Patients must be able and willing to provide written informed consent prior to any&#xD;
             study related procedure being performed. Patients with a legal guardian should be&#xD;
             consented according to local requirements.&#xD;
&#xD;
          5. Patients must be willing and able to take oral medication and able to comply with the&#xD;
             study specific procedures.&#xD;
&#xD;
          6. The patient is in good health as determined by medical examination and based on the&#xD;
             investigator's judgement&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients with any of the following characteristics will be excluded from entering the&#xD;
        study:&#xD;
&#xD;
          1. Patients with PArkinson´s Disease (PD) who have not participated in the randomized&#xD;
             double-blind phase of the previous NMS-Nab Study.&#xD;
&#xD;
          2. Patients that experienced a drug-related SAE or had a (drug-related) moderate or&#xD;
             severe AE during the NMS-Nab Study will be excluded in the study.&#xD;
&#xD;
          3. Patients who are unable or unwilling to comply with the study procedures in the&#xD;
             investigator´s opinion.&#xD;
&#xD;
          4. Patients with any clinically significant or unstable medical or surgical condition at&#xD;
             the Screening / Baseline Visit that may preclude safety and the completion of the&#xD;
             study participation (based on the investigator's judgement).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Department of Neurology - Medical University Innsbruck</name>
      <address>
        <city>Innsbruck</city>
        <state>Tyrol</state>
        <zip>6020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>July 19, 2018</study_first_submitted>
  <study_first_submitted_qc>December 10, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 12, 2018</study_first_posted>
  <results_first_submitted>January 23, 2021</results_first_submitted>
  <results_first_submitted_qc>February 10, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">March 2, 2021</results_first_posted>
  <last_update_submitted>February 10, 2021</last_update_submitted>
  <last_update_submitted_qc>February 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 2, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University Innsbruck</investigator_affiliation>
    <investigator_full_name>Klaus Seppi, MD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Parkinson´s Disease</keyword>
  <keyword>cannabinoids</keyword>
  <keyword>non-motor symptoms</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nabilone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>The results of this study will be published according to the principles of publication policy. There are no arrangements on publication issues with subsiding parties.</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 4, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/96/NCT03773796/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Treatment Group</title>
          <description>Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg&#xD;
Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Summaries of baseline values were produced in patients receiving at least one dose of study medication and completing at least V 1 as per protocol.</population>
      <group_list>
        <group group_id="B1">
          <title>Treatment Group</title>
          <description>Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg&#xD;
Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="21"/>
          </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="67.23" spread="6.15"/>
                  </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="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Disease duration</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9.30" spread="6.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Education</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12.81" spread="2.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>AEs in PD Patients Taking Nabilone, Between V 1 and V 3</title>
        <description>Safety and tolerability will be evaluated with reference to the following:&#xD;
Adverse Events (AE)</description>
        <time_frame>6 months</time_frame>
        <population>primary endpoint was safety, please refer to Adverse events section.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group</title>
            <description>Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg&#xD;
Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis</description>
          </group>
        </group_list>
        <measure>
          <title>AEs in PD Patients Taking Nabilone, Between V 1 and V 3</title>
          <description>Safety and tolerability will be evaluated with reference to the following:&#xD;
Adverse Events (AE)</description>
          <population>primary endpoint was safety, please refer to Adverse events section.</population>
          <units>adverse events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Subjects (%) Who Discontinue the Study Due to an AE Between V 1 and V 3</title>
        <description>Safety and tolerability will be evaluated with reference to the following:&#xD;
Number of subjects (%) who discontinue the study due to an AE The reasons for discontinuation will be grouped in &quot;discontinuation due to an AE&quot; and &quot;discontinuation due to other reasons&quot;. Both results will be provided separately.</description>
        <time_frame>6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group</title>
            <description>Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg&#xD;
Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects (%) Who Discontinue the Study Due to an AE Between V 1 and V 3</title>
          <description>Safety and tolerability will be evaluated with reference to the following:&#xD;
Number of subjects (%) who discontinue the study due to an AE The reasons for discontinuation will be grouped in &quot;discontinuation due to an AE&quot; and &quot;discontinuation due to other reasons&quot;. Both results will be provided separately.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Subjects (%) Who Discontinue the Study Due to Other Reasons Than an AE Between V 1 and V 3</title>
        <description>Safety and tolerability will be evaluated with reference to the following:&#xD;
Number of subjects (%) who discontinue the study due to other reasons than an AE The reasons for discontinuation will be grouped in &quot;discontinuation due to an AE&quot; and &quot;discontinuation due to other reasons&quot;. Both results will be provided separately.</description>
        <time_frame>6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group</title>
            <description>Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg&#xD;
Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects (%) Who Discontinue the Study Due to Other Reasons Than an AE Between V 1 and V 3</title>
          <description>Safety and tolerability will be evaluated with reference to the following:&#xD;
Number of subjects (%) who discontinue the study due to other reasons than an AE The reasons for discontinuation will be grouped in &quot;discontinuation due to an AE&quot; and &quot;discontinuation due to other reasons&quot;. Both results will be provided separately.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Suicidality in PD Patients Taking Nabilone Between V 1 and V 3 Using the Columbia-Suicide Severity Rating Scale</title>
        <description>Change in aggregated data of the Columbia-Suicide Severity Rating Scale (C-SSRS).&#xD;
Different questions for suicidality with the possible answers yes or no. Yes represents a worse outcome. Count of participants with new suicidality is given.</description>
        <time_frame>between V 1 and V 3 (6 months)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group</title>
            <description>Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg&#xD;
Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis</description>
          </group>
        </group_list>
        <measure>
          <title>Suicidality in PD Patients Taking Nabilone Between V 1 and V 3 Using the Columbia-Suicide Severity Rating Scale</title>
          <description>Change in aggregated data of the Columbia-Suicide Severity Rating Scale (C-SSRS).&#xD;
Different questions for suicidality with the possible answers yes or no. Yes represents a worse outcome. Count of participants with new suicidality is given.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Hallucinations in PD Patients Taking Nabilone Between V 1 and V 3</title>
        <description>Changes in points of the:&#xD;
Hallucination item (1.2) of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) Each item has a minimum of 0 and a maximum of 4 points with higher score values representing a worse outcome.&#xD;
Participant count with a change in the hallucination item is reported.</description>
        <time_frame>between V 1 and V 3 (6 months)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group</title>
            <description>Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg&#xD;
Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis</description>
          </group>
        </group_list>
        <measure>
          <title>Hallucinations in PD Patients Taking Nabilone Between V 1 and V 3</title>
          <description>Changes in points of the:&#xD;
Hallucination item (1.2) of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) Each item has a minimum of 0 and a maximum of 4 points with higher score values representing a worse outcome.&#xD;
Participant count with a change in the hallucination item is reported.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>less hallucinations</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>more hallucinations</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>no change</title>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Day-time Sleepiness in PD Patients Taking Nabilone Between V 1 and V 3</title>
        <description>Changes in points of the:&#xD;
Day-time sleepiness item (1.8) of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) Each item has a minimum of 0 and a maximum of 4 points with higher score values representing a worse outcome.</description>
        <time_frame>between V 1 and V 3 (6 months)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group</title>
            <description>Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg&#xD;
Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis</description>
          </group>
        </group_list>
        <measure>
          <title>Day-time Sleepiness in PD Patients Taking Nabilone Between V 1 and V 3</title>
          <description>Changes in points of the:&#xD;
Day-time sleepiness item (1.8) of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) Each item has a minimum of 0 and a maximum of 4 points with higher score values representing a worse outcome.</description>
          <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="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.05" spread="0.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Orthostatic Hypotension in PD Patients Taking Nabilone Between V 1 and V 3</title>
        <description>Changes in points of the:&#xD;
Orthostatic hypotension item (1.12) of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS)&#xD;
Each item has a minimum of 0 and a maximum of 4 points with higher score values representing a worse outcome.</description>
        <time_frame>between V 1 and V 3 (6 months)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group</title>
            <description>Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg&#xD;
Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis</description>
          </group>
        </group_list>
        <measure>
          <title>Orthostatic Hypotension in PD Patients Taking Nabilone Between V 1 and V 3</title>
          <description>Changes in points of the:&#xD;
Orthostatic hypotension item (1.12) of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS)&#xD;
Each item has a minimum of 0 and a maximum of 4 points with higher score values representing a worse outcome.</description>
          <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="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.16" spread="0.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Subject Compliance in PD Patients Taking Nabilone.</title>
        <description>subject incompliance as per drug accountability (%)</description>
        <time_frame>between V 1 and V 3 (6 months)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group</title>
            <description>Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg&#xD;
Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis</description>
          </group>
        </group_list>
        <measure>
          <title>Subject Compliance in PD Patients Taking Nabilone.</title>
          <description>subject incompliance as per drug accountability (%)</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Changes in Supine and Standing Blood Pressure Measurements (mmHg) in PD Patients Taking Nabilone Between V 1 and V 3</title>
        <description>changes in supine and standing blood pressure measurements (mmHg)&#xD;
Row titles:&#xD;
Mean Change of systolic blood pressure readings (SBP) from supine to standing position for 3 min at V 1&#xD;
Mean Change of systolic blood pressure readings (SBP) from supine to standing position for 3 min at V 3&#xD;
Mean Change of diastolic blood pressure readings (DBP) from supine to standing position for 3 min at V 1&#xD;
Mean Change of diastolic blood pressure readings (DBP) from supine to standing position for 3 min at V 3</description>
        <time_frame>between V 1 and V 3 (6 months)</time_frame>
        <population>21 patients for V 1 and 19 for V 3 analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group</title>
            <description>Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg&#xD;
Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in Supine and Standing Blood Pressure Measurements (mmHg) in PD Patients Taking Nabilone Between V 1 and V 3</title>
          <description>changes in supine and standing blood pressure measurements (mmHg)&#xD;
Row titles:&#xD;
Mean Change of systolic blood pressure readings (SBP) from supine to standing position for 3 min at V 1&#xD;
Mean Change of systolic blood pressure readings (SBP) from supine to standing position for 3 min at V 3&#xD;
Mean Change of diastolic blood pressure readings (DBP) from supine to standing position for 3 min at V 1&#xD;
Mean Change of diastolic blood pressure readings (DBP) from supine to standing position for 3 min at V 3</description>
          <population>21 patients for V 1 and 19 for V 3 analyzed.</population>
          <units>mmHg</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_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>1. change of SBP from supine to standing position for 3 min at V 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.14" spread="7.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2. change of SBP from supine to standing position for 3 min at V 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.05" spread="11.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3. change of DBP from supine to standing position for 3 min at V 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.76" spread="6.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4. change of DBP from supine to standing position for 3 min at V 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.42" spread="9.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes in Motor and Non-motor Symptoms in Patients With PD Taking Nabilone Between V 1 and V 3</title>
        <description>Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:&#xD;
Total and different parts of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) Part I: minimum points: 0, maximum points: 52, higher score values indicate a worse outcome.&#xD;
Part II: minimum points: 0, maximum points: 52, higher score values indicate a worse outcome.&#xD;
Part III: minimum points: 0, maximum points: 132, higher score values indicate a worse outcome.&#xD;
Part IV: minimum points: 0, maximum points: 24, higher score values indicate a worse outcome.&#xD;
Total Score: minimum points: 0, maximum points: 272, higher score values indicate a worse outcome.</description>
        <time_frame>between V 1 and V 3 (6 months)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group</title>
            <description>Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg&#xD;
Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in Motor and Non-motor Symptoms in Patients With PD Taking Nabilone Between V 1 and V 3</title>
          <description>Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:&#xD;
Total and different parts of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) Part I: minimum points: 0, maximum points: 52, higher score values indicate a worse outcome.&#xD;
Part II: minimum points: 0, maximum points: 52, higher score values indicate a worse outcome.&#xD;
Part III: minimum points: 0, maximum points: 132, higher score values indicate a worse outcome.&#xD;
Part IV: minimum points: 0, maximum points: 24, higher score values indicate a worse outcome.&#xD;
Total Score: minimum points: 0, maximum points: 272, higher score values indicate a worse outcome.</description>
          <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="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>MDS-UPDRS I</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.58" spread="13.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MDS-UPDRS II</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.58" spread="3.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MDS-UPDRS III</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.89" spread="6.88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MDS-UPDRS IV</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.16" spread="2.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MDS-UPDRS Total Score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.05" spread="15.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes in Non-motor Symptoms (NMSS) in Patients With PD Taking Nabilone Between V 1 and V 3</title>
        <description>Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:&#xD;
Non Motor Symptoms Scale (NMSS) Minimum: 0, maximum: 360, higher score values indicate a worse outcome.</description>
        <time_frame>between V 1 and V 3 (6 months)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group</title>
            <description>Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg&#xD;
Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in Non-motor Symptoms (NMSS) in Patients With PD Taking Nabilone Between V 1 and V 3</title>
          <description>Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:&#xD;
Non Motor Symptoms Scale (NMSS) Minimum: 0, maximum: 360, higher score values indicate a worse outcome.</description>
          <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="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.84" spread="18.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes in Non-motor Symptoms (HADS) in Patients With PD Taking Nabilone Between V 1 and V 3</title>
        <description>Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:&#xD;
Hospital anxiety and depression scale (HADS), HADS-A assesses anxiety, HADS-D depression.&#xD;
Total scale: minimum: 0, maximum: 42, separate HADS-A/-D score: minimum: 0, maximum: 21.&#xD;
Higher score values indicate a worse outcome.</description>
        <time_frame>between V 1 and V 3 (6 months)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group</title>
            <description>Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg&#xD;
Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in Non-motor Symptoms (HADS) in Patients With PD Taking Nabilone Between V 1 and V 3</title>
          <description>Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:&#xD;
Hospital anxiety and depression scale (HADS), HADS-A assesses anxiety, HADS-D depression.&#xD;
Total scale: minimum: 0, maximum: 42, separate HADS-A/-D score: minimum: 0, maximum: 21.&#xD;
Higher score values indicate a worse outcome.</description>
          <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="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>HADS-A</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.16" spread="1.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HADS-D</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.00" spread="2.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes in Quality of Life in Patients With PD Taking Nabilone Between V 1 and V 3</title>
        <description>Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:&#xD;
Parkinson´s Disease Questionnaire - 8 (PDQ-8). Minimum: 0, maximum: 42, higher score values indicate a worse outcome.&#xD;
PDQ-8 was standardized, therefore the score ranges from 0 to 100 (= PDQ-8 Summary Index).</description>
        <time_frame>between V 1 and V 3 (6 months)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group</title>
            <description>Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg&#xD;
Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in Quality of Life in Patients With PD Taking Nabilone Between V 1 and V 3</title>
          <description>Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:&#xD;
Parkinson´s Disease Questionnaire - 8 (PDQ-8). Minimum: 0, maximum: 42, higher score values indicate a worse outcome.&#xD;
PDQ-8 was standardized, therefore the score ranges from 0 to 100 (= PDQ-8 Summary Index).</description>
          <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="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.96" spread="9.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes in Sleepiness in Patients With PD Taking Nabilone Between V 1 and V 3</title>
        <description>Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:&#xD;
Epworth Sleepiness Scale (ESS) Minimum: 0, maximum: 24, higher score values indicate a worse outcome.</description>
        <time_frame>between V 1 and V 3 (6 months)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group</title>
            <description>Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg&#xD;
Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in Sleepiness in Patients With PD Taking Nabilone Between V 1 and V 3</title>
          <description>Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:&#xD;
Epworth Sleepiness Scale (ESS) Minimum: 0, maximum: 24, higher score values indicate a worse outcome.</description>
          <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="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.11" spread="2.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes in Fatigue in Patients With PD Taking Nabilone Between V 1 and V 3</title>
        <description>Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:&#xD;
Fatigue Severity Scale (FSS). Minimum: 9, maximum: 63, higher score values indicate a worse outcome.</description>
        <time_frame>between V 1 and V 3 (6 months)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group</title>
            <description>Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg&#xD;
Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in Fatigue in Patients With PD Taking Nabilone Between V 1 and V 3</title>
          <description>Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:&#xD;
Fatigue Severity Scale (FSS). Minimum: 9, maximum: 63, higher score values indicate a worse outcome.</description>
          <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="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.26" spread="10.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes in Pain in Patients With PD Taking Nabilone Between V 1 and V 3</title>
        <description>Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:&#xD;
King's Parkinson's disease pain scale (KPPS) Minimum: 0, maximum: 168, higher score values indicate a worse outcome.</description>
        <time_frame>between V 1 and V 3 (6 months)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group</title>
            <description>Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg&#xD;
Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in Pain in Patients With PD Taking Nabilone Between V 1 and V 3</title>
          <description>Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:&#xD;
King's Parkinson's disease pain scale (KPPS) Minimum: 0, maximum: 168, higher score values indicate a worse outcome.</description>
          <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="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.84" spread="15.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes in Impulsive-compulsive Behaviour in Patients With PD Taking Nabilone Between V 1 and V 3</title>
        <description>Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:&#xD;
Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) Minimum: 0, maximum: 112, higher score values indicate a worse outcome.</description>
        <time_frame>between V 1 and V 3 (6 months)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group</title>
            <description>Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg&#xD;
Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in Impulsive-compulsive Behaviour in Patients With PD Taking Nabilone Between V 1 and V 3</title>
          <description>Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:&#xD;
Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) Minimum: 0, maximum: 112, higher score values indicate a worse outcome.</description>
          <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="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.11" spread="1.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes in Overall Symptoms in Patients With PD Taking Nabilone Between V 1 and V 3</title>
        <description>Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:&#xD;
Clinical Global Impression - Global Improvement (CGI-I) Minimum: 1, maximum: 7, higher score values indicate a worse outcome.</description>
        <time_frame>between V 1 and V 3 (6 months)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group</title>
            <description>Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg&#xD;
Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in Overall Symptoms in Patients With PD Taking Nabilone Between V 1 and V 3</title>
          <description>Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:&#xD;
Clinical Global Impression - Global Improvement (CGI-I) Minimum: 1, maximum: 7, higher score values indicate a worse outcome.</description>
          <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="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.16" spread="1.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes in Cognitive Function (MoCA) in Patients With PD Taking Nabilone Between V 1 and V 3</title>
        <description>The change of Montreal Cognitive Assessment (MoCA, minimum 0 points, maximum 30 points, higher score values indicate better outcome) score values between the Screening Visit of the NMS-Nab Study (before the first intake of nabilone medication) and the termination visit of this study will be assessed as secondary efficacy endpoints.</description>
        <time_frame>from Screening of the preceding study (NCT03769896) to V 3 of this study (a maximum of 2 years, at study completion)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group</title>
            <description>Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg&#xD;
Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in Cognitive Function (MoCA) in Patients With PD Taking Nabilone Between V 1 and V 3</title>
          <description>The change of Montreal Cognitive Assessment (MoCA, minimum 0 points, maximum 30 points, higher score values indicate better outcome) score values between the Screening Visit of the NMS-Nab Study (before the first intake of nabilone medication) and the termination visit of this study will be assessed as secondary efficacy endpoints.</description>
          <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="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.11" spread="1.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes in Cognitive Function (MMSE) in Patients With PD Taking Nabilone</title>
        <description>The change of Mini Mental State Exam (MMSE, minimum 0 points, maximum 30 points, higher score values indicate better outcome) between the Screening Visit of the NMS-Nab Study (before the first intake of nabilone medication) and the termination visit of this study will be assessed as secondary efficacy endpoints.</description>
        <time_frame>from screening of the preceding study (NCT03769896) to V 3 of this study (a maximum of 2 years, at study completion)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group</title>
            <description>Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg&#xD;
Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in Cognitive Function (MMSE) in Patients With PD Taking Nabilone</title>
          <description>The change of Mini Mental State Exam (MMSE, minimum 0 points, maximum 30 points, higher score values indicate better outcome) between the Screening Visit of the NMS-Nab Study (before the first intake of nabilone medication) and the termination visit of this study will be assessed as secondary efficacy endpoints.</description>
          <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="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.42" spread="1.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Eye-tracking Evaluation in PD Patients Taking Nabilone at Visit V 2 to Assess Changes in Reaction Time.</title>
        <description>Change of the reaction time (seconds), between Screening and Termination Visit of the randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study and V 2 of this study as measured by the Eye-tracking examination.</description>
        <time_frame>a maximum of 2 years, measurement at V2 visit</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Eye-tracking Evaluation in PD Patients Taking Nabilone at Visit V 2 to Assess Changes in Attention Span.</title>
        <description>Change of attention span (error rate, correct trials) between Screening and Termination Visit of the randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study and V 2 of this study as measured by the Eye-tracking examination.</description>
        <time_frame>a maximum of 2 years, measurement at V2 visit</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Eye-tracking Evaluation in PD Patients Taking Nabilone at Visit V 2 to Assess Changes in the Ability to Concentrate.</title>
        <description>Change of ability to concentrate (error rate, correct trials) between Screening and Termination Visit of the randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study and V 2 of this study as measured by the Eye-tracking examination.</description>
        <time_frame>a maximum of 2 years, measurement at V2 visit</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>V1 to V 3, 6 months</time_frame>
      <desc>definitions do not differ&#xD;
Other Adverse Events: This section only covers adverse events that fulfill the following reporting definition (threshold 5%): Other (Not Including Serious) Adverse Events: A table of anticipated and unanticipated events (not included in the serious adverse event table) that exceed a frequency threshold (for example, 5%) within any arm of the clinical study, grouped by organ system, with number and frequency of such events in each arm/group of the clinical study.</desc>
      <group_list>
        <group group_id="E1">
          <title>Treatment Group</title>
          <description>Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg&#xD;
Nabilone 0.25 mg: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedRA</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="22"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title vocab="MedDRA">Vomiting</sub_title>
                <description>hospitalization due to medication-induced nausea and vomiting</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title vocab="MedDRA (Unspecified)">Intervertebral disc protrusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>rectum carcinoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Worsening of Parkinson´s disease symptoms</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>respiratory tract infection</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Osteopenia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Osteoarthropathy</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Concentration difficulties</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>intermittant falls</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>transient numbness of the face</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Worsening of Parkinson´s Disease symptoms</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>Prof. Klaus Seppi</name_or_title>
      <organization>Medical University of Innsbruck</organization>
      <phone>004351250481553</phone>
      <email>klaus.seppi@tirol-kliniken.at</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/NCT03773796
org study id: 1.3
nct id: NCT03773796
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is an open-label extension study for participants of the randomized placebo-controlled,
      double-blind, parallel-group, enriched enrolment randomized withdrawal NMS-Nab Study,
      assessing the long-term safety and efficacy of nabilone for non-motor symptoms in patients
      with Parkinson´s Disease (PD). Nabilone is an analogue of tetrahydrocannabinol (THC), the
      psychoactive component of cannabis. Nabilone acts as a partial agonist on both Cannabinoid 1
      (CB1) and Cannabinoid 2 (CB2) receptor in humans and therefore mimics the effect of THC but
      with more predictable side effects and less euphoria.

      Eligible patients will be re-tapered in an open-label nabilone dose optimization phase
      followed by an open-label period of 6 months on a stable nabilone dose.
This is an open-label extension study for participants of the randomized placebo-controlled,
      double-blind, parallel-group, enriched enrolment randomized withdrawal NMS-Nab Study,
      assessing the long-term safety and efficacy of nabilone for non-motor symptoms in patients
      with Parkinson´s Disease. Nabilone is an analogue of tetrahydrocannabinol (THC), the
      psychoactive component of cannabis.

      Eligible subjects will be re-tapered with open-label nabilone, optimally up to the dose the
      patient had in the NMS-Nab Trial. It is the investigator´s decision to modify this dose, if
      necessary. The re-tapering will be performed up to a maximum dose of 1 mg twice daily.
      Treatment responders will enter the open-label treatment period for 6 months with visits
      being performed every 3 months in the context of the patient´s regularly scheduled visits in
      the specialized outpatient department. The last visit will be the Termination Visit.
      Following this, nabilone will be tapered. During this period the patients will receive phone
      calls every other day. A Safety Follow-Up Visit will be performed.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: open-label
primary purpose: Treatment
masking: None (Open Label)
masking description: None, open-label
measure: AEs in PD Patients Taking Nabilone, Between V 1 and V 3
time frame: 6 months
description: Safety and tolerability will be evaluated with reference to the following:
Adverse Events (AE)
measure: Number of Subjects (%) Who Discontinue the Study Due to an AE Between V 1 and V 3
time frame: 6 months
description: Safety and tolerability will be evaluated with reference to the following:
Number of subjects (%) who discontinue the study due to an AE The reasons for discontinuation will be grouped in "discontinuation due to an AE" and "discontinuation due to other reasons". Both results will be provided separately.
measure: Number of Subjects (%) Who Discontinue the Study Due to Other Reasons Than an AE Between V 1 and V 3
time frame: 6 months
description: Safety and tolerability will be evaluated with reference to the following:
Number of subjects (%) who discontinue the study due to other reasons than an AE The reasons for discontinuation will be grouped in "discontinuation due to an AE" and "discontinuation due to other reasons". Both results will be provided separately.
measure: Suicidality in PD Patients Taking Nabilone Between V 1 and V 3 Using the Columbia-Suicide Severity Rating Scale
time frame: between V 1 and V 3 (6 months)
description: Change in aggregated data of the Columbia-Suicide Severity Rating Scale (C-SSRS).
Different questions for suicidality with the possible answers yes or no. Yes represents a worse outcome. Count of participants with new suicidality is given.
measure: Hallucinations in PD Patients Taking Nabilone Between V 1 and V 3
time frame: between V 1 and V 3 (6 months)
description: Changes in points of the:
Hallucination item (1.2) of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) Each item has a minimum of 0 and a maximum of 4 points with higher score values representing a worse outcome.
Participant count with a change in the hallucination item is reported.
measure: Day-time Sleepiness in PD Patients Taking Nabilone Between V 1 and V 3
time frame: between V 1 and V 3 (6 months)
description: Changes in points of the:
Day-time sleepiness item (1.8) of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) Each item has a minimum of 0 and a maximum of 4 points with higher score values representing a worse outcome.
measure: Orthostatic Hypotension in PD Patients Taking Nabilone Between V 1 and V 3
time frame: between V 1 and V 3 (6 months)
description: Changes in points of the:
Orthostatic hypotension item (1.12) of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS)
Each item has a minimum of 0 and a maximum of 4 points with higher score values representing a worse outcome.
measure: Subject Compliance in PD Patients Taking Nabilone.
time frame: between V 1 and V 3 (6 months)
description: subject incompliance as per drug accountability (%)
measure: Changes in Supine and Standing Blood Pressure Measurements (mmHg) in PD Patients Taking Nabilone Between V 1 and V 3
time frame: between V 1 and V 3 (6 months)
description: changes in supine and standing blood pressure measurements (mmHg)
Row titles:
Mean Change of systolic blood pressure readings (SBP) from supine to standing position for 3 min at V 1
Mean Change of systolic blood pressure readings (SBP) from supine to standing position for 3 min at V 3
Mean Change of diastolic blood pressure readings (DBP) from supine to standing position for 3 min at V 1
Mean Change of diastolic blood pressure readings (DBP) from supine to standing position for 3 min at V 3
measure: Changes in Motor and Non-motor Symptoms in Patients With PD Taking Nabilone Between V 1 and V 3
time frame: between V 1 and V 3 (6 months)
description: Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:
Total and different parts of Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) Part I: minimum points: 0, maximum points: 52, higher score values indicate a worse outcome.
Part II: minimum points: 0, maximum points: 52, higher score values indicate a worse outcome.
Part III: minimum points: 0, maximum points: 132, higher score values indicate a worse outcome.
Part IV: minimum points: 0, maximum points: 24, higher score values indicate a worse outcome.
Total Score: minimum points: 0, maximum points: 272, higher score values indicate a worse outcome.
measure: Changes in Non-motor Symptoms (NMSS) in Patients With PD Taking Nabilone Between V 1 and V 3
time frame: between V 1 and V 3 (6 months)
description: Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:
Non Motor Symptoms Scale (NMSS) Minimum: 0, maximum: 360, higher score values indicate a worse outcome.
measure: Changes in Non-motor Symptoms (HADS) in Patients With PD Taking Nabilone Between V 1 and V 3
time frame: between V 1 and V 3 (6 months)
description: Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:
Hospital anxiety and depression scale (HADS), HADS-A assesses anxiety, HADS-D depression.
Total scale: minimum: 0, maximum: 42, separate HADS-A/-D score: minimum: 0, maximum: 21.
Higher score values indicate a worse outcome.
measure: Changes in Quality of Life in Patients With PD Taking Nabilone Between V 1 and V 3
time frame: between V 1 and V 3 (6 months)
description: Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:
Parkinson´s Disease Questionnaire - 8 (PDQ-8). Minimum: 0, maximum: 42, higher score values indicate a worse outcome.
PDQ-8 was standardized, therefore the score ranges from 0 to 100 (= PDQ-8 Summary Index).
measure: Changes in Sleepiness in Patients With PD Taking Nabilone Between V 1 and V 3
time frame: between V 1 and V 3 (6 months)
description: Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:
Epworth Sleepiness Scale (ESS) Minimum: 0, maximum: 24, higher score values indicate a worse outcome.
measure: Changes in Fatigue in Patients With PD Taking Nabilone Between V 1 and V 3
time frame: between V 1 and V 3 (6 months)
description: Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:
Fatigue Severity Scale (FSS). Minimum: 9, maximum: 63, higher score values indicate a worse outcome.
measure: Changes in Pain in Patients With PD Taking Nabilone Between V 1 and V 3
time frame: between V 1 and V 3 (6 months)
description: Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:
King's Parkinson's disease pain scale (KPPS) Minimum: 0, maximum: 168, higher score values indicate a worse outcome.
measure: Changes in Impulsive-compulsive Behaviour in Patients With PD Taking Nabilone Between V 1 and V 3
time frame: between V 1 and V 3 (6 months)
description: Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:
Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) Minimum: 0, maximum: 112, higher score values indicate a worse outcome.
measure: Changes in Overall Symptoms in Patients With PD Taking Nabilone Between V 1 and V 3
time frame: between V 1 and V 3 (6 months)
description: Long-term efficacy evaluations are the secondary objective of this study. Efficacy endpoints include changes in points from V 1 to the termination visit in the following questionnaires:
Clinical Global Impression - Global Improvement (CGI-I) Minimum: 1, maximum: 7, higher score values indicate a worse outcome.
measure: Changes in Cognitive Function (MoCA) in Patients With PD Taking Nabilone Between V 1 and V 3
time frame: from Screening of the preceding study (NCT03769896) to V 3 of this study (a maximum of 2 years, at study completion)
description: The change of Montreal Cognitive Assessment (MoCA, minimum 0 points, maximum 30 points, higher score values indicate better outcome) score values between the Screening Visit of the NMS-Nab Study (before the first intake of nabilone medication) and the termination visit of this study will be assessed as secondary efficacy endpoints.
measure: Changes in Cognitive Function (MMSE) in Patients With PD Taking Nabilone
time frame: from screening of the preceding study (NCT03769896) to V 3 of this study (a maximum of 2 years, at study completion)
description: The change of Mini Mental State Exam (MMSE, minimum 0 points, maximum 30 points, higher score values indicate better outcome) between the Screening Visit of the NMS-Nab Study (before the first intake of nabilone medication) and the termination visit of this study will be assessed as secondary efficacy endpoints.
measure: Eye-tracking Evaluation in PD Patients Taking Nabilone at Visit V 2 to Assess Changes in Reaction Time.
time frame: a maximum of 2 years, measurement at V2 visit
description: Change of the reaction time (seconds), between Screening and Termination Visit of the randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study and V 2 of this study as measured by the Eye-tracking examination.
measure: Eye-tracking Evaluation in PD Patients Taking Nabilone at Visit V 2 to Assess Changes in Attention Span.
time frame: a maximum of 2 years, measurement at V2 visit
description: Change of attention span (error rate, correct trials) between Screening and Termination Visit of the randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study and V 2 of this study as measured by the Eye-tracking examination.
measure: Eye-tracking Evaluation in PD Patients Taking Nabilone at Visit V 2 to Assess Changes in the Ability to Concentrate.
time frame: a maximum of 2 years, measurement at V2 visit
description: Change of ability to concentrate (error rate, correct trials) between Screening and Termination Visit of the randomized placebo-controlled, double-blind, parallel-group, enriched enrolment randomized withdrawal study and V 2 of this study as measured by the Eye-tracking examination.
arm group label: Treatment Group
arm group type: Other
description: Assessment of long-term efficacy and safety of nabilone 0.25 mg - 2 mg
intervention type: Drug
intervention name: Nabilone 0.25 mg
description: capsules, 0.25 mg up to 2 mg of nabilone taken orally on a daily basis
arm group label: Treatment Group
other name: Canemes
criteria: 
gender: All
minimum age: 30 Years
maximum age: 100 Years
healthy volunteers: No
facility: 
country: Austria
responsible party type: Principal Investigator
investigator affiliation: Medical University Innsbruck
investigator full name: Klaus Seppi, MD
investigator title: Principal Investigator
mesh term: Parkinson Disease
mesh term: Nabilone
sharing ipd: No
ipd description: The results of this study will be published according to the principles of publication policy. There are no arrangements on publication issues with subsiding parties.
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 