<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/NCT02242487</url>
  </required_header>
  <id_info>
    <org_study_id>CVT-301-004E</org_study_id>
    <nct_id>NCT02242487</nct_id>
  </id_info>
  <brief_title>Twelve Month Safety and Efficacy Study of CVT-301 In Parkinson's Disease Patients With OFF Episodes</brief_title>
  <official_title>A 12 Month, Dose-Level Blinded Study Investigating the Safety and Efficacy of CVT 301 (Levodopa Inhalation Powder) in Parkinson's Disease Patients With Motor Response Fluctuations (OFF Phenomena)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Acorda Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Acorda Therapeutics</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is a 12-month, dose-level blinded, multicenter study of 2 inhaled dose levels of&#xD;
      CVT-301 for the treatment of up to 5 OFF episodes per day in PD patients experiencing motor&#xD;
      fluctuations (OFF episodes). All patients will receive active treatment, but patients will be&#xD;
      blinded to dose level. This will serve as an extension to the CVT-301-004 (NCT02240030) study&#xD;
      for those patients who participated in that study and remain eligible for this study. In&#xD;
      addition, patients who previously completed the CVT-301-003 (NCT01777555), CVT-301-009&#xD;
      (NCT02807675) and CVT-301-005 (NCT02352363) (observational arm completers), as well as&#xD;
      CVT-301 naïve patients may be enrolled if they meet the CVT-301-004E eligibility criteria.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>March 2015</start_date>
  <completion_date type="Actual">May 2018</completion_date>
  <primary_completion_date type="Actual">May 2018</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pulmonary Safety of CVT-301 Change From Baseline for FEV1.</measure>
    <time_frame>Change from baseline at 52 weeks</time_frame>
    <description>To characterize the effects of CVT-301 on pulmonary safety, as assessed by spirometry FEV1 (forced expiratory volume in 1 second) by treatment group and Treatment Visit (TV). This study was a 12-month, dose-level blinded, multi-center study of 2 inhaled dose levels of CVT-301 for the treatment of up to 5 OFF periods per day in PD (Parkinson's Disease) patients experiencing motor fluctuations (OFF periods). Baseline is defined as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004 study and as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004E study for the rest of the patients.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pulmonary Safety for CVT-301 Change From Baseline for FVC.</measure>
    <time_frame>Change from baseline at 52 weeks</time_frame>
    <description>To characterize the effects of CVT-301 on pulmonary safety, as assessed by spirometry FVC, (forced vital capacity) by treatment group and Treatment Visit (TV). This study was a 12-month, dose-level blinded, multi-center study of 2 inhaled dose levels of CVT-301 for the treatment of up to 5 OFF periods per day in PD patients experiencing motor fluctuations (OFF periods). Baseline is defined as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004 study and as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004E study for the rest of the patients.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pulmonary Safety for CVT-301 Change From Baseline for (FEV1/FVC).</measure>
    <time_frame>Change from baseline at 52 weeks</time_frame>
    <description>To characterize the effects of CVT-301 on pulmonary safety, as assessed by spirometry FEV1/FVC (FEV1-forced expiratory volume in 1 second and (FVC) forced vital capacity ratio) by treatment group and Treatment Visit (TV). This study was a 12-month, dose-level blinded, multi-center study of 2 inhaled dose levels of CVT-301 for the treatment of up to 5 OFF periods per day in PD (Parkinson's Disease) patients experiencing motor fluctuations (OFF periods). Baseline is defined as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004 study and as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004E study for the rest of the patients.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Count of Patients Achieving Resolution of an OFF to an ON State Within 60 Minutes.</measure>
    <time_frame>At Treatment Visit - TV6 (Week 52)</time_frame>
    <description>Count of patients achieving resolution of an OFF to an ON state within 60 minutes after study drug is administered in the clinic, and maintaining the ON state at 60 minutes after study drug administration (per the examiner's subjective assessment).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in OFF Time.</measure>
    <time_frame>Change from baseline through 12 months duration of outpatient use</time_frame>
    <description>Patient reported total daily OFF time and was assessed by the patient and recorded in the patient Diary. An &quot;OFF state&quot; is defined as the time when medication is not providing benefit with respect to mobility, slowness, and stiffness. OFF episodes may be heralded by non-motor symptoms (e.g., pain, anxiety) prior to the appearance of motor symptoms. Patients will record their ON and OFF states in their diaries at home.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">325</enrollment>
  <condition>Idiopathic Parkinson's Disease</condition>
  <arm_group>
    <arm_group_label>CVT-301 Low Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Capsules of levodopa inhalational powder used up to 5 times/day for OFF episodes for 12 months duration</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CVT-301 High Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Capsules of levodopa inhalational powder used up to 5 times/day for OFF episodes for 12 months duration</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CVT-301</intervention_name>
    <arm_group_label>CVT-301 High Dose</arm_group_label>
    <arm_group_label>CVT-301 Low Dose</arm_group_label>
    <other_name>Inhaled levodopa</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Idiopathic Parkinson's Disease (PD) diagnosed between the ages of 30 and 80 years;&#xD;
&#xD;
          -  Hoehn and Yahr Stage 1-3 in an &quot;on&quot; state;&#xD;
&#xD;
          -  Require levodopa-containing medication regimen at least 3 times during the waking day;&#xD;
&#xD;
          -  Experience motor fluctuations with a minimum of 2 hours of average daily &quot;off&quot; time&#xD;
             per waking day (excluding early morning &quot;off&quot; time) and demonstrate levodopa&#xD;
             responsiveness;&#xD;
&#xD;
          -  Are on stable PD medication regimen;&#xD;
&#xD;
          -  Total daily levodopa (LD) dose &lt;1600 mg/day;&#xD;
&#xD;
          -  Able to perform a spirometry maneuver in the ON and OFF states&#xD;
&#xD;
          -  Normal cognition confirmed by Mini Mental State Examination (MMSE) score ≥25 ;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or lactating females;&#xD;
&#xD;
          -  Previous surgery for PD or plan to have stereotactic surgery during the study period.&#xD;
             Patients who have had deep brain stimulation [DBS] will also be excluded unless the&#xD;
             procedure was performed more than 6 months prior to study enrollment.&#xD;
&#xD;
          -  History of psychotic symptoms requiring treatment, or suicide ideation or attempt&#xD;
             within last year;&#xD;
&#xD;
          -  Known contraindication to the use of levodopa;&#xD;
&#xD;
          -  Any significant condition, severe concurrent disease, abnormality or finding that&#xD;
             would make patients unsuitable or may compromise patient safety;&#xD;
&#xD;
          -  Any any contraindication to performing routine spirometry.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>86 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Charles Oh, MD</last_name>
    <role>Study Director</role>
    <affiliation>Acorda Therapeutics</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Acorda Site #5020</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85259</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5042</name>
      <address>
        <city>Fresno</city>
        <state>California</state>
        <zip>93710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5064</name>
      <address>
        <city>Fullerton</city>
        <state>California</state>
        <zip>92835</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5035</name>
      <address>
        <city>Loma Linda</city>
        <state>California</state>
        <zip>92354</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5027</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5037</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5070</name>
      <address>
        <city>Pasadena</city>
        <state>California</state>
        <zip>91105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5047</name>
      <address>
        <city>Reseda</city>
        <state>California</state>
        <zip>91335</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5068</name>
      <address>
        <city>Santa Ana</city>
        <state>California</state>
        <zip>92705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5069</name>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <zip>90505</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5052</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5046</name>
      <address>
        <city>Atlantis</city>
        <state>Florida</state>
        <zip>33462</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5053</name>
      <address>
        <city>Aventura</city>
        <state>Florida</state>
        <zip>33180</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5013</name>
      <address>
        <city>Boca Raton</city>
        <state>Florida</state>
        <zip>33486</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5016</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5071</name>
      <address>
        <city>Maitland</city>
        <state>Florida</state>
        <zip>32751</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5044</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5060</name>
      <address>
        <city>Palm Beach Gardens</city>
        <state>Florida</state>
        <zip>33410</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5001</name>
      <address>
        <city>Port Charlotte</city>
        <state>Florida</state>
        <zip>33952</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5065</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <zip>33713</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5012</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33613</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5040</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30329</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5025</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5030</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5011</name>
      <address>
        <city>Elk Grove Village</city>
        <state>Illinois</state>
        <zip>60007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5003</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5067</name>
      <address>
        <city>Baton Rouge</city>
        <state>Louisiana</state>
        <zip>70810</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5057</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5056</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5018</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5002</name>
      <address>
        <city>Bingham Farms</city>
        <state>Michigan</state>
        <zip>48025</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5014</name>
      <address>
        <city>West Bloomfield</city>
        <state>Michigan</state>
        <zip>48322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5041</name>
      <address>
        <city>Golden Valley</city>
        <state>Minnesota</state>
        <zip>55427</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5006</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5023</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5028</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <zip>12208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5039</name>
      <address>
        <city>Brooklyn</city>
        <state>New York</state>
        <zip>11203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5031</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5032</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5004</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5038</name>
      <address>
        <city>Syracuse</city>
        <state>New York</state>
        <zip>13210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5048</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5005</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5050</name>
      <address>
        <city>Norwood</city>
        <state>Ohio</state>
        <zip>45212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5062</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5036</name>
      <address>
        <city>Allentown</city>
        <state>Pennsylvania</state>
        <zip>18103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5010</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5058</name>
      <address>
        <city>Willow Grove</city>
        <state>Pennsylvania</state>
        <zip>19090</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5022</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5029</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>372322551</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5019</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5045</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5049</name>
      <address>
        <city>Henrico</city>
        <state>Virginia</state>
        <zip>23226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5059</name>
      <address>
        <city>Virginia Beach</city>
        <state>Virginia</state>
        <zip>23456</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5051</name>
      <address>
        <city>Kirkland</city>
        <state>Washington</state>
        <zip>98034</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5103</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A5A5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5104</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1Y4E9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5105</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5T2S8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5201</name>
      <address>
        <city>Prague</city>
        <zip>10000</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5203</name>
      <address>
        <city>Prague</city>
        <zip>14000</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5305</name>
      <address>
        <city>Gdańsk</city>
        <state>Zappa</state>
        <zip>80462</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5304</name>
      <address>
        <city>Katowice</city>
        <zip>40588</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5303</name>
      <address>
        <city>Krakow</city>
        <zip>30510</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5306</name>
      <address>
        <city>Kraków</city>
        <zip>30349</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5307</name>
      <address>
        <city>Kraków</city>
        <zip>31505</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5302</name>
      <address>
        <city>Lodz</city>
        <zip>90130</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5308</name>
      <address>
        <city>Warsaw</city>
        <zip>00453</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5301</name>
      <address>
        <city>Warsaw</city>
        <zip>01868</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5407</name>
      <address>
        <city>Pamplona</city>
        <state>Navarre</state>
        <zip>31008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5404</name>
      <address>
        <city>Barcelona</city>
        <zip>08026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5406</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5405</name>
      <address>
        <city>Madrid</city>
        <zip>28006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5403</name>
      <address>
        <city>San Sebastián</city>
        <zip>20009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acorda Site #5401</name>
      <address>
        <city>Sant Cugat Del Vallès</city>
        <zip>08190</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Czechia</country>
    <country>Poland</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Czech Republic</country>
  </removed_countries>
  <link>
    <url>http://cvt301.acordatrials.com/en/patient/?src=clinicaltrialsgov004</url>
    <description>Click here for more information about this study:CVT-301-004E</description>
  </link>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>September 15, 2014</study_first_submitted>
  <study_first_submitted_qc>September 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 17, 2014</study_first_posted>
  <results_first_submitted>June 12, 2019</results_first_submitted>
  <results_first_submitted_qc>July 10, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">July 30, 2019</results_first_posted>
  <last_update_submitted>July 30, 2019</last_update_submitted>
  <last_update_submitted_qc>July 30, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Parkinson's Disease</keyword>
  <keyword>Motor fluctuations</keyword>
  <keyword>levodopa</keyword>
  <keyword>inhaled drugs</keyword>
  <keyword>OFF episodes</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>Levodopa</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 7, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/87/NCT02242487/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 29, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/87/NCT02242487/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Safety population - Altogether, 325 patients were randomized and 312 patients received at least 1 dose of study drug and were included in the Safety Population. Thirteen patients were randomized but did not receive study drug.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>CVT-301 Low Dose</title>
          <description>Two capsules of 30 mg each (60 mg total) of levodopa inhalational powder orally inhaled up to 5 times/day for OFF episodes for 12 months duration&#xD;
CVT-301</description>
        </group>
        <group group_id="P2">
          <title>CVT-301 High Dose</title>
          <description>Two capsules of 42 mg each (84 mg total) of levodopa inhalational powder orally inhaled up to 5 times/day for OFF episodes for 12 months duration&#xD;
CVT-301</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="161"/>
                <participants group_id="P2" count="164"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="99"/>
                <participants group_id="P2" count="117"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="62"/>
                <participants group_id="P2" count="47"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other - Miscellaneous</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="37"/>
                <participants group_id="P2" count="19"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Baseline Characteristics of 312 is based on the Safety Population of 325 participants randomized less 13 who were randomized and Not Dosed.</population>
      <group_list>
        <group group_id="B1">
          <title>CVT-301 Low Dose</title>
          <description>60 mg (two capsules of 30 mg) of levodopa inhalational powder used up to 5 times/day for OFF episodes for 12 months duration&#xD;
CVT-301</description>
        </group>
        <group group_id="B2">
          <title>CVT-301 High Dose</title>
          <description>84 mg (two capsules of 42 mg) of levodopa inhalational powder used up to 5 times/day for OFF episodes for 12 months duration&#xD;
CVT-301</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="153"/>
            <count group_id="B2" value="159"/>
            <count group_id="B3" value="312"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="71"/>
                    <measurement group_id="B2" value="80"/>
                    <measurement group_id="B3" value="151"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="82"/>
                    <measurement group_id="B2" value="79"/>
                    <measurement group_id="B3" value="161"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="63.9" spread="8.76"/>
                    <measurement group_id="B2" value="62.9" spread="8.34"/>
                    <measurement group_id="B3" value="63.4" spread="8.55"/>
                  </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="43"/>
                    <measurement group_id="B2" value="40"/>
                    <measurement group_id="B3" value="83"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="110"/>
                    <measurement group_id="B2" value="119"/>
                    <measurement group_id="B3" value="229"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="147"/>
                    <measurement group_id="B2" value="150"/>
                    <measurement group_id="B3" value="297"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Canada</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Czechia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Poland</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                    <measurement group_id="B2" value="45"/>
                    <measurement group_id="B3" value="84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Spain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="100"/>
                    <measurement group_id="B2" value="101"/>
                    <measurement group_id="B3" value="201"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27.65" spread="4.820"/>
                    <measurement group_id="B2" value="27.59" spread="4.790"/>
                    <measurement group_id="B3" value="27.62" spread="4.797"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Pulmonary Safety of CVT-301 Change From Baseline for FEV1.</title>
        <description>To characterize the effects of CVT-301 on pulmonary safety, as assessed by spirometry FEV1 (forced expiratory volume in 1 second) by treatment group and Treatment Visit (TV). This study was a 12-month, dose-level blinded, multi-center study of 2 inhaled dose levels of CVT-301 for the treatment of up to 5 OFF periods per day in PD (Parkinson's Disease) patients experiencing motor fluctuations (OFF periods). Baseline is defined as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004 study and as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004E study for the rest of the patients.</description>
        <time_frame>Change from baseline at 52 weeks</time_frame>
        <population>Safety population - Altogether, 325 patients were randomized and 312 patients received at least 1 dose of study drug and were included in the Safety Population. Thirteen patients were randomized but did not receive study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>CVT-301 DL1</title>
            <description>60 mg (two capsules of 30 mg each) of Levodopa Inhalational Powder (LIP) up to 5 times a day.</description>
          </group>
          <group group_id="O2">
            <title>CVT-301 DL2</title>
            <description>84 mg (two capsules of 42 mg each) of Levodopa inhalation powder (LIP) up to 5 times a day.</description>
          </group>
        </group_list>
        <measure>
          <title>Pulmonary Safety of CVT-301 Change From Baseline for FEV1.</title>
          <description>To characterize the effects of CVT-301 on pulmonary safety, as assessed by spirometry FEV1 (forced expiratory volume in 1 second) by treatment group and Treatment Visit (TV). This study was a 12-month, dose-level blinded, multi-center study of 2 inhaled dose levels of CVT-301 for the treatment of up to 5 OFF periods per day in PD (Parkinson's Disease) patients experiencing motor fluctuations (OFF periods). Baseline is defined as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004 study and as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004E study for the rest of the patients.</description>
          <population>Safety population - Altogether, 325 patients were randomized and 312 patients received at least 1 dose of study drug and were included in the Safety Population. Thirteen patients were randomized but did not receive study drug.</population>
          <units>Liters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="153"/>
                <count group_id="O2" value="159"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="153"/>
                    <count group_id="O2" value="159"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.957" spread="0.6995"/>
                    <measurement group_id="O2" value="3.117" spread="0.7735"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TV3 (Week 12)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="141"/>
                    <count group_id="O2" value="149"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.059" spread="0.2321"/>
                    <measurement group_id="O2" value="-0.078" spread="0.2108"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TV4 (Week 24)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="119"/>
                    <count group_id="O2" value="136"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.057" spread="0.1999"/>
                    <measurement group_id="O2" value="-0.058" spread="0.2136"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TV5 (Week 36)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="112"/>
                    <count group_id="O2" value="125"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.076" spread="0.2155"/>
                    <measurement group_id="O2" value="-0.052" spread="0.2096"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TV6 (Week 52)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="105"/>
                    <count group_id="O2" value="115"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.086" spread="0.2238"/>
                    <measurement group_id="O2" value="-0.097" spread="0.2230"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pulmonary Safety for CVT-301 Change From Baseline for FVC.</title>
        <description>To characterize the effects of CVT-301 on pulmonary safety, as assessed by spirometry FVC, (forced vital capacity) by treatment group and Treatment Visit (TV). This study was a 12-month, dose-level blinded, multi-center study of 2 inhaled dose levels of CVT-301 for the treatment of up to 5 OFF periods per day in PD patients experiencing motor fluctuations (OFF periods). Baseline is defined as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004 study and as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004E study for the rest of the patients.</description>
        <time_frame>Change from baseline at 52 weeks</time_frame>
        <population>Safety Population - Safety population - Altogether, 325 patients were randomized and 312 patients received at least 1 dose of study drug and were included in the Safety Population. Thirteen patients were randomized but did not receive study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>CVT-301 DL1</title>
            <description>60 mg (two capsules of 30 mg each) of Levodopa Inhalational Powder (LIP) up to 5 times a day.</description>
          </group>
          <group group_id="O2">
            <title>CVT-301 DL2</title>
            <description>84 mg (two capsules of 42 mg each) of Levodopa inhalation powder (LIP) up to 5 times a day.</description>
          </group>
        </group_list>
        <measure>
          <title>Pulmonary Safety for CVT-301 Change From Baseline for FVC.</title>
          <description>To characterize the effects of CVT-301 on pulmonary safety, as assessed by spirometry FVC, (forced vital capacity) by treatment group and Treatment Visit (TV). This study was a 12-month, dose-level blinded, multi-center study of 2 inhaled dose levels of CVT-301 for the treatment of up to 5 OFF periods per day in PD patients experiencing motor fluctuations (OFF periods). Baseline is defined as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004 study and as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004E study for the rest of the patients.</description>
          <population>Safety Population - Safety population - Altogether, 325 patients were randomized and 312 patients received at least 1 dose of study drug and were included in the Safety Population. Thirteen patients were randomized but did not receive study drug.</population>
          <units>Liter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="153"/>
                <count group_id="O2" value="159"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="153"/>
                    <count group_id="O2" value="159"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.840" spread="0.9047"/>
                    <measurement group_id="O2" value="4.045" spread="0.9811"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TV3 (Week 12)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="141"/>
                    <count group_id="O2" value="149"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.064" spread="0.2575"/>
                    <measurement group_id="O2" value="-0.086" spread="0.2667"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TV4 (Week 24)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="119"/>
                    <count group_id="O2" value="136"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.053" spread="0.2710"/>
                    <measurement group_id="O2" value="-0.062" spread="0.2688"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TV5 (Week 36)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="112"/>
                    <count group_id="O2" value="125"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.089" spread="0.3051"/>
                    <measurement group_id="O2" value="-0.050" spread="0.2659"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TV6 (Week 52)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="105"/>
                    <count group_id="O2" value="115"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.106" spread="0.2866"/>
                    <measurement group_id="O2" value="-0.089" spread="0.2747"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pulmonary Safety for CVT-301 Change From Baseline for (FEV1/FVC).</title>
        <description>To characterize the effects of CVT-301 on pulmonary safety, as assessed by spirometry FEV1/FVC (FEV1-forced expiratory volume in 1 second and (FVC) forced vital capacity ratio) by treatment group and Treatment Visit (TV). This study was a 12-month, dose-level blinded, multi-center study of 2 inhaled dose levels of CVT-301 for the treatment of up to 5 OFF periods per day in PD (Parkinson's Disease) patients experiencing motor fluctuations (OFF periods). Baseline is defined as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004 study and as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004E study for the rest of the patients.</description>
        <time_frame>Change from baseline at 52 weeks</time_frame>
        <population>Safety Population - Safety population - Altogether, 325 patients were randomized and 312 patients received at least 1 dose of study drug and were included in the Safety Population. Thirteen patients were randomized but did not receive study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>CVT-301 DL1</title>
            <description>60 mg (two capsules of 30 mg each) of Levodopa Inhalational Powder (LIP) up to 5 times a day.</description>
          </group>
          <group group_id="O2">
            <title>CVT-301 DL2</title>
            <description>84 mg (two capsules of 42 mg each) of Levodopa inhalation powder (LIP) up to 5 times a day.</description>
          </group>
        </group_list>
        <measure>
          <title>Pulmonary Safety for CVT-301 Change From Baseline for (FEV1/FVC).</title>
          <description>To characterize the effects of CVT-301 on pulmonary safety, as assessed by spirometry FEV1/FVC (FEV1-forced expiratory volume in 1 second and (FVC) forced vital capacity ratio) by treatment group and Treatment Visit (TV). This study was a 12-month, dose-level blinded, multi-center study of 2 inhaled dose levels of CVT-301 for the treatment of up to 5 OFF periods per day in PD (Parkinson's Disease) patients experiencing motor fluctuations (OFF periods). Baseline is defined as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004 study and as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004E study for the rest of the patients.</description>
          <population>Safety Population - Safety population - Altogether, 325 patients were randomized and 312 patients received at least 1 dose of study drug and were included in the Safety Population. Thirteen patients were randomized but did not receive study drug.</population>
          <units>Ratio %</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="153"/>
                <count group_id="O2" value="159"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="153"/>
                    <count group_id="O2" value="159"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="77.2" spread="5.24"/>
                    <measurement group_id="O2" value="77.2" spread="6.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TV3 (Week 12)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="141"/>
                    <count group_id="O2" value="149"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.2" spread="3.35"/>
                    <measurement group_id="O2" value="-0.3" spread="2.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TV4 (Week 24)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="119"/>
                    <count group_id="O2" value="136"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" spread="3.64"/>
                    <measurement group_id="O2" value="-0.3" spread="2.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TV5 (Week 36)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="112"/>
                    <count group_id="O2" value="125"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" spread="2.75"/>
                    <measurement group_id="O2" value="-0.3" spread="3.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TV6 (Week 52)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="105"/>
                    <count group_id="O2" value="115"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.2" spread="3.36"/>
                    <measurement group_id="O2" value="-0.7" spread="3.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Count of Patients Achieving Resolution of an OFF to an ON State Within 60 Minutes.</title>
        <description>Count of patients achieving resolution of an OFF to an ON state within 60 minutes after study drug is administered in the clinic, and maintaining the ON state at 60 minutes after study drug administration (per the examiner's subjective assessment).</description>
        <time_frame>At Treatment Visit - TV6 (Week 52)</time_frame>
        <population>ITT (Intent-to-Treat) Population</population>
        <group_list>
          <group group_id="O1">
            <title>CVT-301 DL1</title>
            <description>60 mg (two capsules of 30 mg each) of Levodopa Inhalational Powder (LIP) up to 5 times a day.</description>
          </group>
          <group group_id="O2">
            <title>CVT-301 DL2</title>
            <description>84 mg (two capsules of 42 mg each) of Levodopa inhalation powder (LIP) up to 5 times a day.</description>
          </group>
        </group_list>
        <measure>
          <title>Count of Patients Achieving Resolution of an OFF to an ON State Within 60 Minutes.</title>
          <description>Count of patients achieving resolution of an OFF to an ON state within 60 minutes after study drug is administered in the clinic, and maintaining the ON state at 60 minutes after study drug administration (per the examiner's subjective assessment).</description>
          <population>ITT (Intent-to-Treat) Population</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="144"/>
                <count group_id="O2" value="153"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="78"/>
                    <measurement group_id="O2" value="92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in OFF Time.</title>
        <description>Patient reported total daily OFF time and was assessed by the patient and recorded in the patient Diary. An &quot;OFF state&quot; is defined as the time when medication is not providing benefit with respect to mobility, slowness, and stiffness. OFF episodes may be heralded by non-motor symptoms (e.g., pain, anxiety) prior to the appearance of motor symptoms. Patients will record their ON and OFF states in their diaries at home.</description>
        <time_frame>Change from baseline through 12 months duration of outpatient use</time_frame>
        <population>ITT - (Intent-to-Treat) Population. Patients who discontinue the study prior to a treatment visit are not included in the analysis for that treatment visit. Therefore, the number of patients decreases with each successive treatment visit.</population>
        <group_list>
          <group group_id="O1">
            <title>CVT-301 DL1</title>
            <description>60 mg (two capsules of 30 mg each) of Levodopa Inhalation Powder (LIP)</description>
          </group>
          <group group_id="O2">
            <title>CVT-301 DL2</title>
            <description>84 mg (two capsules of 42 mg each) of Levodopa inhalation powder (LIP)</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in OFF Time.</title>
          <description>Patient reported total daily OFF time and was assessed by the patient and recorded in the patient Diary. An &quot;OFF state&quot; is defined as the time when medication is not providing benefit with respect to mobility, slowness, and stiffness. OFF episodes may be heralded by non-motor symptoms (e.g., pain, anxiety) prior to the appearance of motor symptoms. Patients will record their ON and OFF states in their diaries at home.</description>
          <population>ITT - (Intent-to-Treat) Population. Patients who discontinue the study prior to a treatment visit are not included in the analysis for that treatment visit. Therefore, the number of patients decreases with each successive treatment visit.</population>
          <units>Hours</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="144"/>
                <count group_id="O2" value="153"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TV2 (Week 4)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="137"/>
                    <count group_id="O2" value="143"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.33" spread="0.221"/>
                    <measurement group_id="O2" value="-0.55" spread="0.217"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TV3 (Week 12)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="133"/>
                    <count group_id="O2" value="139"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.23" spread="0.232"/>
                    <measurement group_id="O2" value="-0.38" spread="0.227"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TV4 (Week 24)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="114"/>
                    <count group_id="O2" value="130"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.65" spread="0.235"/>
                    <measurement group_id="O2" value="-0.73" spread="0.227"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TV5 (Week 36)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                    <count group_id="O2" value="116"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.49" spread="0.238"/>
                    <measurement group_id="O2" value="-0.92" spread="0.230"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TV6 (Week 52)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="94"/>
                    <count group_id="O2" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.70" spread="0.239"/>
                    <measurement group_id="O2" value="-0.88" spread="0.229"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>12-month period</time_frame>
      <group_list>
        <group group_id="E1">
          <title>CVT-301 Low Dose</title>
          <description>60 mg (two capsules of 30 mg each) of Levodopa Inhalational Powder (LIP) up to 5 times a day for OFF episodes for 12 months duration.</description>
        </group>
        <group group_id="E2">
          <title>CVT-301 HIgh Dose</title>
          <description>84 mg (two capsules of 42 mg each) of Levodopa inhalation powder (LIP) up to 5 times a day for OFF episodes for 12 months duration.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 20.1</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="153"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="153"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="159"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Mycardial infarction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Sinus node dysfunction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="159"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Goitre</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="159"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Inguinal hernia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Intestinal obstruction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Megacolon</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Naseau</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Oesophageal achalasia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Vomititng</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="159"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="159"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Clostridium difficile infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Hepatitis C</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Necrotising soft tissue infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="159"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Hip fracture</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Radius fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Concussion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Femoral neck fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Rib fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Wound dehiscence</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="159"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="159"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Intervertebral disc protrusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Intervertebral disc degeneration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Osteoporotic fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Spinal column stenosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="159"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Prostrate cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Prostrate cancer metastatic</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="159"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Central nervous system lesion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Metabolic encephalopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Parkinson's disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="159"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Product Issues</title>
            <event_list>
              <event>
                <sub_title>Device connection tissue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="159"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Impulse-control disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Suicide threat</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="159"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="159"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Bone graft</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="159"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 20.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="81" subjects_at_risk="153"/>
                <counts group_id="E2" subjects_affected="69" subjects_at_risk="159"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="10" subjects_affected="10" subjects_at_risk="153"/>
                <counts group_id="E2" events="13" subjects_affected="12" subjects_at_risk="159"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="153"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="159"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="26" subjects_affected="24" subjects_at_risk="153"/>
                <counts group_id="E2" events="22" subjects_affected="17" subjects_at_risk="159"/>
              </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="9" subjects_affected="8" subjects_at_risk="153"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="159"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dyskinesia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="153"/>
                <counts group_id="E2" events="11" subjects_affected="10" subjects_at_risk="159"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="28" subjects_affected="25" subjects_at_risk="153"/>
                <counts group_id="E2" events="27" subjects_affected="23" subjects_at_risk="159"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding the study results for a period up to 30 days from the date the communication is submitted to the sponsor. The sponsor shall have the right to defer proposed publication an additional 60 days from the end of the review period. The sponsor cannot require changes to the communication and cannot unilaterally extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Charles Oh, Senior Vice President - Clinical Development</name_or_title>
      <organization>Acorda Therapeutics</organization>
      <phone>914-326-5455</phone>
      <email>coh@acorda.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02242487
org study id: CVT-301-004E
nct id: NCT02242487
lead sponsor: 
has dmc: Yes
This study is a 12-month, dose-level blinded, multicenter study of 2 inhaled dose levels of
      CVT-301 for the treatment of up to 5 OFF episodes per day in PD patients experiencing motor
      fluctuations (OFF episodes). All patients will receive active treatment, but patients will be
      blinded to dose level. This will serve as an extension to the CVT-301-004 (NCT02240030) study
      for those patients who participated in that study and remain eligible for this study. In
      addition, patients who previously completed the CVT-301-003 (NCT01777555), CVT-301-009
      (NCT02807675) and CVT-301-005 (NCT02352363) (observational arm completers), as well as
      CVT-301 naïve patients may be enrolled if they meet the CVT-301-004E eligibility criteria.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pulmonary Safety of CVT-301 Change From Baseline for FEV1.
time frame: Change from baseline at 52 weeks
description: To characterize the effects of CVT-301 on pulmonary safety, as assessed by spirometry FEV1 (forced expiratory volume in 1 second) by treatment group and Treatment Visit (TV). This study was a 12-month, dose-level blinded, multi-center study of 2 inhaled dose levels of CVT-301 for the treatment of up to 5 OFF periods per day in PD (Parkinson's Disease) patients experiencing motor fluctuations (OFF periods). Baseline is defined as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004 study and as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004E study for the rest of the patients.
measure: Pulmonary Safety for CVT-301 Change From Baseline for FVC.
time frame: Change from baseline at 52 weeks
description: To characterize the effects of CVT-301 on pulmonary safety, as assessed by spirometry FVC, (forced vital capacity) by treatment group and Treatment Visit (TV). This study was a 12-month, dose-level blinded, multi-center study of 2 inhaled dose levels of CVT-301 for the treatment of up to 5 OFF periods per day in PD patients experiencing motor fluctuations (OFF periods). Baseline is defined as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004 study and as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004E study for the rest of the patients.
measure: Pulmonary Safety for CVT-301 Change From Baseline for (FEV1/FVC).
time frame: Change from baseline at 52 weeks
description: To characterize the effects of CVT-301 on pulmonary safety, as assessed by spirometry FEV1/FVC (FEV1-forced expiratory volume in 1 second and (FVC) forced vital capacity ratio) by treatment group and Treatment Visit (TV). This study was a 12-month, dose-level blinded, multi-center study of 2 inhaled dose levels of CVT-301 for the treatment of up to 5 OFF periods per day in PD (Parkinson's Disease) patients experiencing motor fluctuations (OFF periods). Baseline is defined as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004 study and as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004E study for the rest of the patients.
measure: Count of Patients Achieving Resolution of an OFF to an ON State Within 60 Minutes.
time frame: At Treatment Visit - TV6 (Week 52)
description: Count of patients achieving resolution of an OFF to an ON state within 60 minutes after study drug is administered in the clinic, and maintaining the ON state at 60 minutes after study drug administration (per the examiner's subjective assessment).
measure: Change From Baseline in OFF Time.
time frame: Change from baseline through 12 months duration of outpatient use
description: Patient reported total daily OFF time and was assessed by the patient and recorded in the patient Diary. An "OFF state" is defined as the time when medication is not providing benefit with respect to mobility, slowness, and stiffness. OFF episodes may be heralded by non-motor symptoms (e.g., pain, anxiety) prior to the appearance of motor symptoms. Patients will record their ON and OFF states in their diaries at home.
arm group label: CVT-301 Low Dose
arm group type: Experimental
description: Capsules of levodopa inhalational powder used up to 5 times/day for OFF episodes for 12 months duration
arm group label: CVT-301 High Dose
arm group type: Experimental
description: Capsules of levodopa inhalational powder used up to 5 times/day for OFF episodes for 12 months duration
intervention type: Drug
intervention name: CVT-301
arm group label: CVT-301 High Dose
arm group label: CVT-301 Low Dose
other name: Inhaled levodopa
criteria: 
gender: All
minimum age: 30 Years
maximum age: 86 Years
healthy volunteers: No
last name: Charles Oh, MD
role: Study Director
affiliation: Acorda Therapeutics
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country: Canada
country: Czechia
country: Poland
country: Spain
country: United States
country: Czech Republic
url: http://cvt301.acordatrials.com/en/patient/?src=clinicaltrialsgov004
description: Click here for more information about this study:CVT-301-004E
responsible party type: Sponsor
mesh term: Parkinson Disease
mesh term: Levodopa
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