<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/NCT02228590</url>
  </required_header>
  <id_info>
    <org_study_id>CTH-105</org_study_id>
    <nct_id>NCT02228590</nct_id>
  </id_info>
  <brief_title>A Study to Examine APL-130277 in Patients With Parkinson's Disease</brief_title>
  <official_title>A Phase 2 Study to Examine the Safety, Tolerability and Efficacy of APL-130277 in Patients With Parkinson's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sumitomo Pharma America, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sumitomo Pharma America, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to evaluate the efficacy, tolerability and safety of&#xD;
      single treatments of APL-130277 in 16 patients with Parkinson's Disease (PD)&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 31, 2014</start_date>
  <completion_date type="Actual">November 24, 2014</completion_date>
  <primary_completion_date type="Actual">November 24, 2014</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The Percentage of Patients With Resolution of an 'OFF' Episode to an 'ON' State Following Administration of APL-130277</measure>
    <time_frame>At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.</time_frame>
    <description>Clinical confirmation of an 'OFF' state was assessed prior to dosing and confirmation of 'OFF' or 'ON' was assessed after dosing at Visits 3 - 5 by the Investigator. The first full 'ON' dose was defined as the earliest dose in which a patient achieved a full 'ON' state as assessed by the Investigator. The percentage of patients who achieved their first full 'ON' is presented for each timepoint, regardless of the dose received, and for the study overall (i.e. all post-dose timepoints).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to 'ON' State From Time of Dosing of APL-130277</measure>
    <time_frame>At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.</time_frame>
    <description>Clinical confirmation of 'OFF' or 'ON' was assessed after dosing at Visits 3 - 5 by the Investigator. The time to the full 'ON' state from the time of dosing in minutes was calculated from timings noted by the Investigator and recorded in the electronic case report form (eCRF). The mean time taken for a patient to reach their first full 'ON' state following administration of APL-130277 is presented for patients who turned 'ON' for the study overall.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Duration of 'ON' Response From Time of Dosing of APL-130277</measure>
    <time_frame>At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.</time_frame>
    <description>Clinical confirmation of 'OFF' or 'ON' was assessed after dosing at Visits 3 - 5 by the Investigator. The duration of the 'ON' response was defined as the length of time in which a patient was confirmed 'ON' within a dose, and was calculated from the time noted by the Investigator and recorded in the eCRF. The mean duration of the first full 'ON' response following administration of APL-130277 is presented for patients who turned 'ON' for the study overall.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Patients Who Completed the Trial and Experienced an 'ON' Episode</measure>
    <time_frame>At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.</time_frame>
    <description>Clinical confirmation of 'OFF' or 'ON' was assessed after dosing at Visits 3 - 5 by the Investigator. For the overall study, the percentage of patients who completed the trial, and who experienced an 'ON' episode is presented.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic (PK) Evaluation: Maximum Observed Plasma Concentration (Cmax)</measure>
    <time_frame>Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.</time_frame>
    <description>The mean Cmax values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available.&#xD;
Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay, with a lower limit of quantification of 0.020 nanograms per millilitre (ng/mL).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PK Evaluation: Time of Maximum Observed Plasma Concentration (Tmax)</measure>
    <time_frame>Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.</time_frame>
    <description>The median Tmax values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available.&#xD;
Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated LC-MS/MS assay, with a lower limit of quantification of 0.020 ng/mL.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PK Evaluation: Time to Last Analytically Quantifiable Concentration (Tlast)</measure>
    <time_frame>Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.</time_frame>
    <description>The mean Tlast values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available.&#xD;
Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated LC-MS/MS assay, with a lower limit of quantification of 0.020 ng/mL.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to 90 Minutes (AUC0-90)</measure>
    <time_frame>Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.</time_frame>
    <description>The mean AUC0-90 values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available.&#xD;
Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated LC-MS/MS assay, with a lower limit of quantification of 0.020 ng/mL.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to the Last Measurable Non-zero Concentration (AUClast)</measure>
    <time_frame>Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.</time_frame>
    <description>The mean AUClast values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available.&#xD;
Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated LC-MS/MS assay, with a lower limit of quantification of 0.020 ng/mL. The AUClast was calculated by a combination of linear and logarithmic trapezoidal methods (linear up/log down method).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage Change in MDS-UPDRS Section III Score From Pre-dose Assessment</measure>
    <time_frame>At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.</time_frame>
    <description>The Motor Function section (Section III) of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) included 33 scores based on 18-items, each anchored with 5 responses: 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The scale range was from 0 to 132, with a lower score indicating better motor function and a higher score indicating more severe motor symptoms. The percent change in the MDS-UPDRS Section III score from pre-dose to the first full ON dose or last dose for non-responders is presented. A negative change from baseline indicates an improvement.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Parkinson's Disease</condition>
  <arm_group>
    <arm_group_label>APL-130277</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>open label baseline comparison</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>APL-130277</intervention_name>
    <description>Apomorphine Hydrochloride, Sublingual Thin Film</description>
    <arm_group_label>APL-130277</arm_group_label>
    <other_name>Apomorphine Hydrochloride, Sublingual Thin Film</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female ≥18 years of age.&#xD;
&#xD;
          2. Clinical diagnosis of Idiopathic PD&#xD;
&#xD;
          3. Receiving stable doses of L-dopa +/- other adjunctive PD therapy for at least 4 weeks&#xD;
             before study participation.&#xD;
&#xD;
          4. At least one OFF episode per day and a total daily OFF time of &gt; 2 hours duration.&#xD;
&#xD;
          5. Experience predictable OFF episodes in the morning on awakening prior to receiving&#xD;
             morning dose of levodopa.&#xD;
&#xD;
          6. Stage I to III on the Hoehn and Yahr scale in the &quot;ON&quot; state.&#xD;
&#xD;
          7. If female and of childbearing potential, must agree to use one of the following&#xD;
             methods of birth control:&#xD;
&#xD;
          8. Willing and able to comply with scheduled visits, treatment plan, laboratory tests,&#xD;
             and other study-related procedures to complete the study.&#xD;
&#xD;
          9. Able to understand the consent form, and to provide written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Atypical or secondary parkinsonism&#xD;
&#xD;
          2. Changes in L-dopa or other PD drug dosing regimens 4 weeks before the screening visit.&#xD;
&#xD;
          3. Past treatment with any form of apomorphine within 30 days of Dosing Day 1 (patients&#xD;
             who stopped apomorphine for reasons other than lack of efficacy OR tolerability issues&#xD;
             may be considered for the trial).&#xD;
&#xD;
          4. Female who is pregnant or lactating.&#xD;
&#xD;
          5. Contraindications to APOKYN or hypersensitive to apomorphine hydrochloride or any of&#xD;
             the ingredients of APOKYN (notably sodium metabisulfite), or Tigan®.&#xD;
&#xD;
          6. Participation in any other clinical trial within 14 days of the screening visit.&#xD;
&#xD;
          7. Receipt of any investigational (i.e., unapproved) medication within 30 days of the&#xD;
             screening visit.&#xD;
&#xD;
          8. Currently taking, or likely to need to take at any time during the course of the study&#xD;
&#xD;
          9. Currently taking dopamine antagonists or depleting drugs excluding anticholinergics&#xD;
             and/or antihistamines with anticholinergic effects.&#xD;
&#xD;
         10. Drug or alcohol dependency in the past 6 months.&#xD;
&#xD;
         11. Clinically significant orthostatic hypotension.&#xD;
&#xD;
         12. Malignant melanoma or a history of previously treated malignant melanoma within 5&#xD;
             years.&#xD;
&#xD;
         13. Clinically significant medical surgical or laboratory abnormality in the judgment of&#xD;
             the investigator.&#xD;
&#xD;
         14. Psychiatric disorder, including but not limited to dementia or any disorder that, in&#xD;
             the opinion of the Investigator requires ongoing treatment that would make study&#xD;
             participation unsafe or make treatment compliance difficult.&#xD;
&#xD;
         15. Dementia that precludes providing informed consent.&#xD;
&#xD;
         16. Potential for lack of compliance and follow-up in the judgment of the investigator.&#xD;
&#xD;
         17. Any other condition, current therapy, or prior therapy (within 30 days of the&#xD;
             screening visit), which, in the opinion of the Investigator, would make the subject&#xD;
             unsuitable for the study.&#xD;
&#xD;
         18. Previous neurosurgery for PD.&#xD;
&#xD;
         19. Donation of blood or plasma in the 30 days prior to dosing.&#xD;
&#xD;
         20. Presence of cankers or mouth sores.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>CNS Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Sumitomo Pharma America, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Banner Sun Health Research Institute</name>
      <address>
        <city>Sun City</city>
        <state>Arizona</state>
        <zip>85351</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Movement Disorders Center</name>
      <address>
        <city>Englewood</city>
        <state>Colorado</state>
        <zip>80113</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Parkinson's Disease and Movement Disorders Center of Boca Raton</name>
      <address>
        <city>Boca Raton</city>
        <state>Florida</state>
        <zip>33486</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of South Florida Parkinson's Disease and Movement Disorders Center</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33613</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>August 26, 2014</study_first_submitted>
  <study_first_submitted_qc>August 27, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 29, 2014</study_first_posted>
  <results_first_submitted>June 19, 2020</results_first_submitted>
  <results_first_submitted_qc>July 14, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">July 30, 2020</results_first_posted>
  <disposition_first_submitted>June 24, 2015</disposition_first_submitted>
  <disposition_first_submitted_qc>July 20, 2015</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">August 7, 2015</disposition_first_posted>
  <last_update_submitted>July 14, 2020</last_update_submitted>
  <last_update_submitted_qc>July 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Parkinson's Disease</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>Apomorphine</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>September 10, 2014</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/90/NCT02228590/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 2, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/90/NCT02228590/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Patients with moderate to advanced Idiopathic Parkinson's Disease (PD) were recruited to this study in 4 study sites in the United States from August 2014. The study was completed in November 2014.</recruitment_details>
      <pre_assignment_details>23 patients were screened, 20 were assigned to treatment and 1 withdrew consent prior to treatment. 19 received APL-130277&#xD;
APL-130277 sublingual film for the acute intermittent treatement of OFF episodes in PD patients&#xD;
. Doses studied were 10, 15, 20, 25 and 30 milligrams (mg).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>APL-130277</title>
          <description>At each dosing visit patients were assessed in a 'OFF' state by withholding their PD medication the night before, a dose of APL-130277 was administered. If the patient did not convert to a full 'ON' state within 3 hours and did not experience orthostatic hypotension, the next higher dose of APL-130277 was administered. If the patient did not turn ON with the next higher dose, levodopa was administered and completed their visit. Possible administered doses of APL-130277 were 10, 15, 20, 25 and 30 mg. Dosing Day 1: The starting dose was 10 mg APL-130277, and if no response 15 mg was administered. Dosing Day 2: Either the dose which elicited a response (i.e. an 'ON' state) at Day 1 was administered or the next higher dose (20 mg) was given. If no response occurred at 20 mg APL-130277, 25 mg was administered. Dosing Day 3: Either the dose which elicited a response at Day 2 was administered or the next higher dose (30 mg). If no response occurred at 30 mg the patient was discontinued.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>APL-130277</title>
          <description>At each dosing visit patients were assessed in a 'OFF' state by withholding their PD medication the night before, a dose of APL-130277 was administered. If the patient did not convert to a full 'ON' state within 3 hours and did not experience orthostatic hypotension, the next higher dose of APL-130277 was administered. If the patient did not turn ON with the next higher dose, levodopa was administered and completed their visit. Possible administered doses of APL-130277 were 10, 15, 20, 25 and 30 mg. Dosing Day 1: The starting dose was 10 mg APL-130277, and if no response 15 mg was administered. Dosing Day 2: Either the dose which elicited a response (i.e. an 'ON' state) at Day 1 was administered or the next higher dose (20 mg) was given. If no response occurred at 20 mg APL-130277, 25 mg was administered. Dosing Day 3: Either the dose which elicited a response at Day 2 was administered or the next higher dose (30 mg). If no response occurred at 30 mg the patient was discontinued.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="19"/>
          </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_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </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="61.5" spread="8.71"/>
                  </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="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>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_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Percentage of Patients With Resolution of an 'OFF' Episode to an 'ON' State Following Administration of APL-130277</title>
        <description>Clinical confirmation of an 'OFF' state was assessed prior to dosing and confirmation of 'OFF' or 'ON' was assessed after dosing at Visits 3 - 5 by the Investigator. The first full 'ON' dose was defined as the earliest dose in which a patient achieved a full 'ON' state as assessed by the Investigator. The percentage of patients who achieved their first full 'ON' is presented for each timepoint, regardless of the dose received, and for the study overall (i.e. all post-dose timepoints).</description>
        <time_frame>At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.</time_frame>
        <population>The modified Intent-to-Treat (mITT) Population consisted of all patients who received at least 1 dose of study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>APL-130277</title>
            <description>At each dosing visit patients were assessed in a 'OFF' state by withholding their PD medication the night before, a dose of APL-130277 was administered. If the patient did not convert to a full 'ON' state within 3 hours and did not experience orthostatic hypotension, the next higher dose of APL-130277 was administered. If the patient did not turn ON with the next higher dose, levodopa was administered and completed their visit. Possible administered doses of APL-130277 were 10, 15, 20, 25 and 30 mg. Dosing Day 1: The starting dose was 10 mg APL-130277, and if no response 15 mg was administered. Dosing Day 2: Either the dose which elicited a response (i.e. an 'ON' state) at Day 1 was administered or the next higher dose (20 mg) was given. If no response occurred at 20 mg APL-130277, 25 mg was administered. Dosing Day 3: Either the dose which elicited a response at Day 2 was administered or the next higher dose (30 mg). If no response occurred at 30 mg the patient was discontinued.</description>
          </group>
        </group_list>
        <measure>
          <title>The Percentage of Patients With Resolution of an 'OFF' Episode to an 'ON' State Following Administration of APL-130277</title>
          <description>Clinical confirmation of an 'OFF' state was assessed prior to dosing and confirmation of 'OFF' or 'ON' was assessed after dosing at Visits 3 - 5 by the Investigator. The first full 'ON' dose was defined as the earliest dose in which a patient achieved a full 'ON' state as assessed by the Investigator. The percentage of patients who achieved their first full 'ON' is presented for each timepoint, regardless of the dose received, and for the study overall (i.e. all post-dose timepoints).</description>
          <population>The modified Intent-to-Treat (mITT) Population consisted of all patients who received at least 1 dose of study medication.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Overall</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="78.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>15 minutes post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>30 minutes post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="78.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>45 minutes post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>60 minutes post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>90 minutes post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Time to 'ON' State From Time of Dosing of APL-130277</title>
        <description>Clinical confirmation of 'OFF' or 'ON' was assessed after dosing at Visits 3 - 5 by the Investigator. The time to the full 'ON' state from the time of dosing in minutes was calculated from timings noted by the Investigator and recorded in the electronic case report form (eCRF). The mean time taken for a patient to reach their first full 'ON' state following administration of APL-130277 is presented for patients who turned 'ON' for the study overall.</description>
        <time_frame>At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.</time_frame>
        <population>The mITT Population consisted of all patients who received at least 1 dose of study medication, and data is presented for patients who turned 'ON'.</population>
        <group_list>
          <group group_id="O1">
            <title>APL-130277</title>
            <description>At each dosing visit patients were assessed in a 'OFF' state by withholding their PD medication the night before, a dose of APL-130277 was administered. If the patient did not convert to a full 'ON' state within 3 hours and did not experience orthostatic hypotension, the next higher dose of APL-130277 was administered. If the patient did not turn ON with the next higher dose, levodopa was administered and completed their visit. Possible administered doses of APL-130277 were 10, 15, 20, 25 and 30 mg. Dosing Day 1: The starting dose was 10 mg APL-130277, and if no response 15 mg was administered. Dosing Day 2: Either the dose which elicited a response (i.e. an 'ON' state) at Day 1 was administered or the next higher dose (20 mg) was given. If no response occurred at 20 mg APL-130277, 25 mg was administered. Dosing Day 3: Either the dose which elicited a response at Day 2 was administered or the next higher dose (30 mg). If no response occurred at 30 mg the patient was discontinued.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to 'ON' State From Time of Dosing of APL-130277</title>
          <description>Clinical confirmation of 'OFF' or 'ON' was assessed after dosing at Visits 3 - 5 by the Investigator. The time to the full 'ON' state from the time of dosing in minutes was calculated from timings noted by the Investigator and recorded in the electronic case report form (eCRF). The mean time taken for a patient to reach their first full 'ON' state following administration of APL-130277 is presented for patients who turned 'ON' for the study overall.</description>
          <population>The mITT Population consisted of all patients who received at least 1 dose of study medication, and data is presented for patients who turned 'ON'.</population>
          <units>minutes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.0" spread="7.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Duration of 'ON' Response From Time of Dosing of APL-130277</title>
        <description>Clinical confirmation of 'OFF' or 'ON' was assessed after dosing at Visits 3 - 5 by the Investigator. The duration of the 'ON' response was defined as the length of time in which a patient was confirmed 'ON' within a dose, and was calculated from the time noted by the Investigator and recorded in the eCRF. The mean duration of the first full 'ON' response following administration of APL-130277 is presented for patients who turned 'ON' for the study overall.</description>
        <time_frame>At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.</time_frame>
        <population>The mITT Population consisted of all patients who received at least 1 dose of study medication, and data is presented for patients who turned 'ON'.</population>
        <group_list>
          <group group_id="O1">
            <title>APL-130277</title>
            <description>At each dosing visit patients were assessed in a 'OFF' state by withholding their PD medication the night before, a dose of APL-130277 was administered. If the patient did not convert to a full 'ON' state within 3 hours and did not experience orthostatic hypotension, the next higher dose of APL-130277 was administered. If the patient did not turn ON with the next higher dose, levodopa was administered and completed their visit. Possible administered doses of APL-130277 were 10, 15, 20, 25 and 30 mg. Dosing Day 1: The starting dose was 10 mg APL-130277, and if no response 15 mg was administered. Dosing Day 2: Either the dose which elicited a response (i.e. an 'ON' state) at Day 1 was administered or the next higher dose (20 mg) was given. If no response occurred at 20 mg APL-130277, 25 mg was administered. Dosing Day 3: Either the dose which elicited a response at Day 2 was administered or the next higher dose (30 mg). If no response occurred at 30 mg the patient was discontinued.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of 'ON' Response From Time of Dosing of APL-130277</title>
          <description>Clinical confirmation of 'OFF' or 'ON' was assessed after dosing at Visits 3 - 5 by the Investigator. The duration of the 'ON' response was defined as the length of time in which a patient was confirmed 'ON' within a dose, and was calculated from the time noted by the Investigator and recorded in the eCRF. The mean duration of the first full 'ON' response following administration of APL-130277 is presented for patients who turned 'ON' for the study overall.</description>
          <population>The mITT Population consisted of all patients who received at least 1 dose of study medication, and data is presented for patients who turned 'ON'.</population>
          <units>minutes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50.0" spread="19.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Patients Who Completed the Trial and Experienced an 'ON' Episode</title>
        <description>Clinical confirmation of 'OFF' or 'ON' was assessed after dosing at Visits 3 - 5 by the Investigator. For the overall study, the percentage of patients who completed the trial, and who experienced an 'ON' episode is presented.</description>
        <time_frame>At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.</time_frame>
        <population>The mITT Population consisted of all patients who received at least 1 dose of study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>APL-130277</title>
            <description>At each dosing visit patients were assessed in a 'OFF' state by withholding their PD medication the night before, a dose of APL-130277 was administered. If the patient did not convert to a full 'ON' state within 3 hours and did not experience orthostatic hypotension, the next higher dose of APL-130277 was administered. If the patient did not turn ON with the next higher dose, levodopa was administered and completed their visit. Possible administered doses of APL-130277 were 10, 15, 20, 25 and 30 mg. Dosing Day 1: The starting dose was 10 mg APL-130277, and if no response 15 mg was administered. Dosing Day 2: Either the dose which elicited a response (i.e. an 'ON' state) at Day 1 was administered or the next higher dose (20 mg) was given. If no response occurred at 20 mg APL-130277, 25 mg was administered. Dosing Day 3: Either the dose which elicited a response at Day 2 was administered or the next higher dose (30 mg). If no response occurred at 30 mg the patient was discontinued.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients Who Completed the Trial and Experienced an 'ON' Episode</title>
          <description>Clinical confirmation of 'OFF' or 'ON' was assessed after dosing at Visits 3 - 5 by the Investigator. For the overall study, the percentage of patients who completed the trial, and who experienced an 'ON' episode is presented.</description>
          <population>The mITT Population consisted of all patients who received at least 1 dose of study medication.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="78.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetic (PK) Evaluation: Maximum Observed Plasma Concentration (Cmax)</title>
        <description>The mean Cmax values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available.&#xD;
Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay, with a lower limit of quantification of 0.020 nanograms per millilitre (ng/mL).</description>
        <time_frame>Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.</time_frame>
        <population>Blood draws for APL-130277 PK analyses were collected at select sites only. The PK Population consisted of all patients who had sufficient concentration-time data to derive noncompartmental PK parameters.</population>
        <group_list>
          <group group_id="O1">
            <title>APL-130277</title>
            <description>At each dosing visit patients were assessed in a 'OFF' state by withholding their PD medication the night before, a dose of APL-130277 was administered. If the patient did not convert to a full 'ON' state within 3 hours and did not experience orthostatic hypotension, the next higher dose of APL-130277 was administered. If the patient did not turn ON with the next higher dose, levodopa was administered and completed their visit. Possible administered doses of APL-130277 were 10, 15, 20, 25 and 30 mg. Dosing Day 1: The starting dose was 10 mg APL-130277, and if no response 15 mg was administered. Dosing Day 2: Either the dose which elicited a response (i.e. an 'ON' state) at Day 1 was administered or the next higher dose (20 mg) was given. If no response occurred at 20 mg APL-130277, 25 mg was administered. Dosing Day 3: Either the dose which elicited a response at Day 2 was administered or the next higher dose (30 mg). If no response occurred at 30 mg the patient was discontinued.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic (PK) Evaluation: Maximum Observed Plasma Concentration (Cmax)</title>
          <description>The mean Cmax values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available.&#xD;
Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay, with a lower limit of quantification of 0.020 nanograms per millilitre (ng/mL).</description>
          <population>Blood draws for APL-130277 PK analyses were collected at select sites only. The PK Population consisted of all patients who had sufficient concentration-time data to derive noncompartmental PK parameters.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>10 mg APL-130277 Dose 1 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.01" spread="0.914"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>15 mg APL-130277 Dose 2 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.52" spread="1.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>10 mg APL-130277 Dose 1 Day 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.18" spread="NA">No SD is available as data is for a single patient.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20 mg APL-130277 Dose 1 Day 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.82" spread="1.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>25 mg APL-130277 Dose 2 Day 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.84" spread="NA">No SD available due to small number of patients analysed for this dose</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20 mg APL-130277 Dose 1 Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.82" spread="1.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>25 mg APL-130277 Dose 1 Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.3" spread="NA">No SD is available as data is for a single patient.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>30 mg APL-130277 Dose 1 Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.22" spread="NA">No SD is available as data is for a single patient.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>25 mg APL-130277 Dose 2 Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.84" spread="2.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>PK Evaluation: Time of Maximum Observed Plasma Concentration (Tmax)</title>
        <description>The median Tmax values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available.&#xD;
Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated LC-MS/MS assay, with a lower limit of quantification of 0.020 ng/mL.</description>
        <time_frame>Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.</time_frame>
        <population>Blood draws for APL-130277 PK analyses were collected at select sites only. The PK Population consisted of all patients who had sufficient concentration-time data to derive noncompartmental PK parameters.</population>
        <group_list>
          <group group_id="O1">
            <title>APL-130277</title>
            <description>At each dosing visit patients were assessed in a 'OFF' state by withholding their PD medication the night before, a dose of APL-130277 was administered. If the patient did not convert to a full 'ON' state within 3 hours and did not experience orthostatic hypotension, the next higher dose of APL-130277 was administered. If the patient did not turn ON with the next higher dose, levodopa was administered and completed their visit. Possible administered doses of APL-130277 were 10, 15, 20, 25 and 30 mg. Dosing Day 1: The starting dose was 10 mg APL-130277, and if no response 15 mg was administered. Dosing Day 2: Either the dose which elicited a response (i.e. an 'ON' state) at Day 1 was administered or the next higher dose (20 mg) was given. If no response occurred at 20 mg APL-130277, 25 mg was administered. Dosing Day 3: Either the dose which elicited a response at Day 2 was administered or the next higher dose (30 mg). If no response occurred at 30 mg the patient was discontinued.</description>
          </group>
        </group_list>
        <measure>
          <title>PK Evaluation: Time of Maximum Observed Plasma Concentration (Tmax)</title>
          <description>The median Tmax values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available.&#xD;
Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated LC-MS/MS assay, with a lower limit of quantification of 0.020 ng/mL.</description>
          <population>Blood draws for APL-130277 PK analyses were collected at select sites only. The PK Population consisted of all patients who had sufficient concentration-time data to derive noncompartmental PK parameters.</population>
          <units>minutes</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>10 mg APL-130277 Dose 1 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60.0" lower_limit="45.0" upper_limit="90.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>15 mg APL-130277 Dose 2 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.0" lower_limit="24.0" upper_limit="90.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20 mg APL-130277 Dose 1 Day 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.0" lower_limit="25.0" upper_limit="61.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20 mg APL-130277 Dose 1 Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="56.5" lower_limit="30.0" upper_limit="61.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>25 mg APL-130277 Dose 2 Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.0" lower_limit="28.0" upper_limit="90.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>PK Evaluation: Time to Last Analytically Quantifiable Concentration (Tlast)</title>
        <description>The mean Tlast values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available.&#xD;
Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated LC-MS/MS assay, with a lower limit of quantification of 0.020 ng/mL.</description>
        <time_frame>Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.</time_frame>
        <population>Blood draws for APL-130277 PK analyses were collected at select sites only. The PK Population consisted of all patients who had sufficient concentration-time data to derive noncompartmental PK parameters.</population>
        <group_list>
          <group group_id="O1">
            <title>APL-130277</title>
            <description>At each dosing visit patients were assessed in a 'OFF' state by withholding their PD medication the night before, a dose of APL-130277 was administered. If the patient did not convert to a full 'ON' state within 3 hours and did not experience orthostatic hypotension, the next higher dose of APL-130277 was administered. If the patient did not turn ON with the next higher dose, levodopa was administered and completed their visit. Possible administered doses of APL-130277 were 10, 15, 20, 25 and 30 mg. Dosing Day 1: The starting dose was 10 mg APL-130277, and if no response 15 mg was administered. Dosing Day 2: Either the dose which elicited a response (i.e. an 'ON' state) at Day 1 was administered or the next higher dose (20 mg) was given. If no response occurred at 20 mg APL-130277, 25 mg was administered. Dosing Day 3: Either the dose which elicited a response at Day 2 was administered or the next higher dose (30 mg). If no response occurred at 30 mg the patient was discontinued.</description>
          </group>
        </group_list>
        <measure>
          <title>PK Evaluation: Time to Last Analytically Quantifiable Concentration (Tlast)</title>
          <description>The mean Tlast values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available.&#xD;
Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated LC-MS/MS assay, with a lower limit of quantification of 0.020 ng/mL.</description>
          <population>Blood draws for APL-130277 PK analyses were collected at select sites only. The PK Population consisted of all patients who had sufficient concentration-time data to derive noncompartmental PK parameters.</population>
          <units>minutes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>10 mg APL-130277 Dose 1 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="89.4" spread="8.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>15 mg APL-130277 Dose 2 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90.8" spread="2.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>10 mg APL-130277 Dose 1 Day 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="95.0" spread="NA">No SD is available as data is for a single patient.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20 mg APL-130277 Dose 1 Day 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="88.9" spread="15.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>25 mg APL-130277 Dose 2 Day 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="94.0" spread="NA">No SD available due to small number patients analysed for this dose.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20 mg APL-130277 Dose 1 Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="95.2" spread="6.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>25 mg APL-130277 Dose 1 Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="102" spread="NA">No SD is available as data is for a single patient</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>30 mg APL-130277 Dose 1 Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92.0" spread="NA">No SD is available as data is for a single patient</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>25 mg APL-130277 Dose 2 Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="75.7" spread="24.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to 90 Minutes (AUC0-90)</title>
        <description>The mean AUC0-90 values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available.&#xD;
Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated LC-MS/MS assay, with a lower limit of quantification of 0.020 ng/mL.</description>
        <time_frame>Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.</time_frame>
        <population>Blood draws for APL-130277 PK analyses were collected at select sites only. The PK Population consisted of all patients who had sufficient concentration-time data to derive noncompartmental PK parameters.</population>
        <group_list>
          <group group_id="O1">
            <title>APL-130277</title>
            <description>At each dosing visit patients were assessed in a 'OFF' state by withholding their PD medication the night before, a dose of APL-130277 was administered. If the patient did not convert to a full 'ON' state within 3 hours and did not experience orthostatic hypotension, the next higher dose of APL-130277 was administered. If the patient did not turn ON with the next higher dose, levodopa was administered and completed their visit. Possible administered doses of APL-130277 were 10, 15, 20, 25 and 30 mg. Dosing Day 1: The starting dose was 10 mg APL-130277, and if no response 15 mg was administered. Dosing Day 2: Either the dose which elicited a response (i.e. an 'ON' state) at Day 1 was administered or the next higher dose (20 mg) was given. If no response occurred at 20 mg APL-130277, 25 mg was administered. Dosing Day 3: Either the dose which elicited a response at Day 2 was administered or the next higher dose (30 mg). If no response occurred at 30 mg the patient was discontinued.</description>
          </group>
        </group_list>
        <measure>
          <title>PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to 90 Minutes (AUC0-90)</title>
          <description>The mean AUC0-90 values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available.&#xD;
Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated LC-MS/MS assay, with a lower limit of quantification of 0.020 ng/mL.</description>
          <population>Blood draws for APL-130277 PK analyses were collected at select sites only. The PK Population consisted of all patients who had sufficient concentration-time data to derive noncompartmental PK parameters.</population>
          <units>min*ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>10 mg APL-130277 Dose 1 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="132" spread="42.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>15 mg APL-130277 Dose 2 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="149" spread="57.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>10 mg APL-130277 Dose 1 Day 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="269" spread="NA">No SD is available as data is for a single patient</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20 mg APL-130277 Dose 1 Day 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="216" spread="127"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>25 mg APL-130277 Dose 2 Day 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="266" spread="NA">No SD available due to small number patients analysed for this dose.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20 mg APL-130277 Dose 1 Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="170" spread="77.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>25 mg APl-130277 Dose 1 Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="507" spread="NA">No SD is available as data is for a single patient</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>30 mg APL-130277 Dose 1 Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="197" spread="NA">No SD is available as data is for a single patient</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>25 mg APL-130277 Dose 2 Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="367" spread="NA">No SD available due to small number patients analysed for this dose.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to the Last Measurable Non-zero Concentration (AUClast)</title>
        <description>The mean AUClast values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available.&#xD;
Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated LC-MS/MS assay, with a lower limit of quantification of 0.020 ng/mL. The AUClast was calculated by a combination of linear and logarithmic trapezoidal methods (linear up/log down method).</description>
        <time_frame>Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.</time_frame>
        <population>Blood draws for APL-130277 PK analyses were collected at select sites only. The PK Population consisted of all patients who had sufficient concentration-time data to derive noncompartmental PK parameters.</population>
        <group_list>
          <group group_id="O1">
            <title>APL-130277</title>
            <description>At each dosing visit patients were assessed in a 'OFF' state by withholding their PD medication the night before, a dose of APL-130277 was administered. If the patient did not convert to a full 'ON' state within 3 hours and did not experience orthostatic hypotension, the next higher dose of APL-130277 was administered. If the patient did not turn ON with the next higher dose, levodopa was administered and completed their visit. Possible administered doses of APL-130277 were 10, 15, 20, 25 and 30 mg. Dosing Day 1: The starting dose was 10 mg APL-130277, and if no response 15 mg was administered. Dosing Day 2: Either the dose which elicited a response (i.e. an 'ON' state) at Day 1 was administered or the next higher dose (20 mg) was given. If no response occurred at 20 mg APL-130277, 25 mg was administered. Dosing Day 3: Either the dose which elicited a response at Day 2 was administered or the next higher dose (30 mg). If no response occurred at 30 mg the patient was discontinued.</description>
          </group>
        </group_list>
        <measure>
          <title>PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to the Last Measurable Non-zero Concentration (AUClast)</title>
          <description>The mean AUClast values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available.&#xD;
Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated LC-MS/MS assay, with a lower limit of quantification of 0.020 ng/mL. The AUClast was calculated by a combination of linear and logarithmic trapezoidal methods (linear up/log down method).</description>
          <population>Blood draws for APL-130277 PK analyses were collected at select sites only. The PK Population consisted of all patients who had sufficient concentration-time data to derive noncompartmental PK parameters.</population>
          <units>min*ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>10 mg APL-130277 Dose 1 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="121" spread="52.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>15 mg APL-130277 Dose 2 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="151" spread="58.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>10 mg APL-130277 Dose 1 Day 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="279" spread="NA">No SD is available as data is for a single patient</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20 mg APL-130277 Dose 1 Day 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="203" spread="122"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>25 mg APL-130277 Dose 2 Day 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="277" spread="NA">No SD available due to small number patients analysed for this dose.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20 mg APL-130277 Dose 1 Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="179" spread="69.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>25 mg APl-130277 Dose 1 Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="566" spread="NA">No SD is available as data is for a single patient</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>30 mg APl-130277 Dose 1 Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="206" spread="NA">No SD is available as data is for a single patient</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>25 mg APL-130277 Dose 2 Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="268" spread="193"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage Change in MDS-UPDRS Section III Score From Pre-dose Assessment</title>
        <description>The Motor Function section (Section III) of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) included 33 scores based on 18-items, each anchored with 5 responses: 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The scale range was from 0 to 132, with a lower score indicating better motor function and a higher score indicating more severe motor symptoms. The percent change in the MDS-UPDRS Section III score from pre-dose to the first full ON dose or last dose for non-responders is presented. A negative change from baseline indicates an improvement.</description>
        <time_frame>At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.</time_frame>
        <population>The mITT Population consisted of all patients who received at least 1 dose of study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>APL-130277</title>
            <description>At each of 3 dosing visits patients were assessed in a practically defined 'OFF' state after withholding their usual PD medications the night before and APL-130277 sublingual film was administered initially at 10 mg. If the patient did not convert to a full 'ON' state within 3 hours from initial dosing and did not experience orthostatic</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage Change in MDS-UPDRS Section III Score From Pre-dose Assessment</title>
          <description>The Motor Function section (Section III) of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) included 33 scores based on 18-items, each anchored with 5 responses: 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The scale range was from 0 to 132, with a lower score indicating better motor function and a higher score indicating more severe motor symptoms. The percent change in the MDS-UPDRS Section III score from pre-dose to the first full ON dose or last dose for non-responders is presented. A negative change from baseline indicates an improvement.</description>
          <population>The mITT Population consisted of all patients who received at least 1 dose of study medication.</population>
          <units>percent of change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Pre-Dose to 15 min Post-Dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-27.9" spread="20.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Pre-Dose to 30 min Post-Dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-34.4" spread="19.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Pre-Dose to 45 min Post-Dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-35.6" spread="20.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Pre-Dose to 60 min Post-Dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-32.4" spread="23.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Pre-Dose to 90 min Post-Dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-23.8" spread="26.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Treatment-emergent adverse events (AEs) were collected over a timeframe of approximately 3 months, with an onset at the time of or following the start of treatment with study medication and prior to 7 days after the end of treatment, or AEs which started prior to treatment but worsened at the time of or following the start of treatment.</time_frame>
      <desc>Adverse events are presented for the Safety Population which consisted of all patients who were enrolled into the study and received at least 1 dose of study medication.</desc>
      <group_list>
        <group group_id="E1">
          <title>APL-130277</title>
          <description>At each of 3 dosing visits patients were assessed in a practically defined 'OFF' state after withholding their usual PD medications the night before and APL-130277 sublingual film was administered initially at 10 mg. If the patient did not convert to a full 'ON' state within 3 hours from initial dosing and did not experience orthostatic</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MeDRA 17.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
              </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="19"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <default_vocab>MeDRA 17.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>nausea</sub_title>
                <counts group_id="E1" events="8" subjects_affected="4" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>chest discomfort</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>muscle spasms</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>muscuar weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>musculoskeletal stiffness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>neck pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>balance disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>dizziness</sub_title>
                <counts group_id="E1" events="8" subjects_affected="7" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>headache</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>paraesthesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>somnolence</sub_title>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>tremor</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>apathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>nervousness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>yawning</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>upper-airway cough syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>hyperhidrosis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>hot flush</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>orthostatic hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>peripheral coldness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="19"/>
              </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>In the event the Study is part of a multi-center study, the first publication of the results of the Study shall be made in conjunction with the results of other participating study sites as a mult-center publication; provided however, if a mult-center publication is not forthcoming within twenty-four (24) months following completion of the Study at all sites, institution and Investigator shall be free to publish.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Due to the 90-minute sampling estimate λz values or calculate AUCinf, AUCext, or half-life as stated in the protocol was not possible.No PK parameters were calculated for subjects with fewer than 4 quantifiable concentrations following BLQ imputation</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>CNS Medical Director</name_or_title>
      <organization>Sunovion Pharmaceuticals Inc.</organization>
      <phone>866-503-6351</phone>
      <email>clinicaltrialdisclosure@sunovion.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/NCT02228590
org study id: CTH-105
nct id: NCT02228590
lead sponsor: 
has dmc: No
The primary objective of this study is to evaluate the efficacy, tolerability and safety of
      single treatments of APL-130277 in 16 patients with Parkinson's Disease (PD)
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The Percentage of Patients With Resolution of an 'OFF' Episode to an 'ON' State Following Administration of APL-130277
time frame: At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.
description: Clinical confirmation of an 'OFF' state was assessed prior to dosing and confirmation of 'OFF' or 'ON' was assessed after dosing at Visits 3 - 5 by the Investigator. The first full 'ON' dose was defined as the earliest dose in which a patient achieved a full 'ON' state as assessed by the Investigator. The percentage of patients who achieved their first full 'ON' is presented for each timepoint, regardless of the dose received, and for the study overall (i.e. all post-dose timepoints).
measure: Time to 'ON' State From Time of Dosing of APL-130277
time frame: At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.
description: Clinical confirmation of 'OFF' or 'ON' was assessed after dosing at Visits 3 - 5 by the Investigator. The time to the full 'ON' state from the time of dosing in minutes was calculated from timings noted by the Investigator and recorded in the electronic case report form (eCRF). The mean time taken for a patient to reach their first full 'ON' state following administration of APL-130277 is presented for patients who turned 'ON' for the study overall.
measure: Duration of 'ON' Response From Time of Dosing of APL-130277
time frame: At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.
description: Clinical confirmation of 'OFF' or 'ON' was assessed after dosing at Visits 3 - 5 by the Investigator. The duration of the 'ON' response was defined as the length of time in which a patient was confirmed 'ON' within a dose, and was calculated from the time noted by the Investigator and recorded in the eCRF. The mean duration of the first full 'ON' response following administration of APL-130277 is presented for patients who turned 'ON' for the study overall.
measure: Percentage of Patients Who Completed the Trial and Experienced an 'ON' Episode
time frame: At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.
description: Clinical confirmation of 'OFF' or 'ON' was assessed after dosing at Visits 3 - 5 by the Investigator. For the overall study, the percentage of patients who completed the trial, and who experienced an 'ON' episode is presented.
measure: Pharmacokinetic (PK) Evaluation: Maximum Observed Plasma Concentration (Cmax)
time frame: Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.
description: The mean Cmax values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available.
Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay, with a lower limit of quantification of 0.020 nanograms per millilitre (ng/mL).
measure: PK Evaluation: Time of Maximum Observed Plasma Concentration (Tmax)
time frame: Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.
description: The median Tmax values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available.
Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated LC-MS/MS assay, with a lower limit of quantification of 0.020 ng/mL.
measure: PK Evaluation: Time to Last Analytically Quantifiable Concentration (Tlast)
time frame: Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.
description: The mean Tlast values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available.
Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated LC-MS/MS assay, with a lower limit of quantification of 0.020 ng/mL.
measure: PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to 90 Minutes (AUC0-90)
time frame: Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.
description: The mean AUC0-90 values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available.
Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated LC-MS/MS assay, with a lower limit of quantification of 0.020 ng/mL.
measure: PK Evaluation: Area Under the Plasma Concentration Time Curve, From Time 0 to the Last Measurable Non-zero Concentration (AUClast)
time frame: Just prior to dosing and at 10, 20, 30, 45, 60 and 90 minutes after each dose at Visits 3 - 5.
description: The mean AUClast values are presented for each dosage administered at Visits 3, 4, and 5 for which data was available.
Plasma concentrations of the active substance of APL-130277, apomorphine, were analysed using a validated LC-MS/MS assay, with a lower limit of quantification of 0.020 ng/mL. The AUClast was calculated by a combination of linear and logarithmic trapezoidal methods (linear up/log down method).
measure: Percentage Change in MDS-UPDRS Section III Score From Pre-dose Assessment
time frame: At 15, 30, 45, 60 and 90 minutes after dosing at Visits 3 - 5.
description: The Motor Function section (Section III) of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) included 33 scores based on 18-items, each anchored with 5 responses: 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The scale range was from 0 to 132, with a lower score indicating better motor function and a higher score indicating more severe motor symptoms. The percent change in the MDS-UPDRS Section III score from pre-dose to the first full ON dose or last dose for non-responders is presented. A negative change from baseline indicates an improvement.
arm group label: APL-130277
arm group type: Other
description: open label baseline comparison
intervention type: Drug
intervention name: APL-130277
description: Apomorphine Hydrochloride, Sublingual Thin Film
arm group label: APL-130277
other name: Apomorphine Hydrochloride, Sublingual Thin Film
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: CNS Medical Director
role: Study Director
affiliation: Sumitomo Pharma America, Inc.
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Parkinson Disease
mesh term: Apomorphine
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Due to the 90-minute sampling estimate λz values or calculate AUCinf, AUCext, or half-life as stated in the protocol was not possible.No PK parameters were calculated for subjects with fewer than 4 quantifiable concentrations following BLQ imputation
point of contact: 