<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/NCT03250117</url>
  </required_header>
  <id_info>
    <org_study_id>ROP-001</org_study_id>
    <nct_id>NCT03250117</nct_id>
  </id_info>
  <brief_title>Relative Bioavailability Study of Ropinirole Implants in Parkinson's Patients on L-Dopa Switched From Oral Ropinirole</brief_title>
  <official_title>An Open-Label, Relative Bioavailability Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Ropinirole Implants in Patients With Parkinson's Disease Switched From Oral Immediate-Release Ropinirole While on L-Dopa</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Titan Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Titan Pharmaceuticals</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Subjects stable on L-Dopa and oral ropinirole will have their ropinirole replaced with the&#xD;
      Ropinirole Implant(s). The Ropinirole Implant was designed using the ProNeura™ implant&#xD;
      technology where the implant is inserted under the skin. This study will measure how much&#xD;
      ropinirole is released in the blood during 12 weeks of ropinirole implant treatment, and&#xD;
      evaluate the side effects of this new formulation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    This study was terminated for reasons not related to efficacy or safety&#xD;
  </why_stopped>
  <start_date type="Actual">October 10, 2017</start_date>
  <completion_date type="Actual">May 22, 2018</completion_date>
  <primary_completion_date type="Actual">May 22, 2018</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Subjects receive oral immediate release (IR) ropinirole for 7-10 days, and then are switched to ropinirole implant(s) for 12 weeks.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC0-24 Hours of Ropinirole</measure>
    <time_frame>0-24 hours</time_frame>
    <description>Area under the plasma drug concentration-time curve of ropinirole</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Total Number of Adverse Events Across Participants</measure>
    <time_frame>0-12 weeks</time_frame>
    <description>Safety and tolerability of ropinirole implant(s) presented as the total number of adverse events experienced by the analysis population.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>AUC0-24 Hours of N-despropyl Ropinirole</measure>
    <time_frame>0-24 hours</time_frame>
    <description>Area under the plasma drug concentration-time curve of N-despropyl ropinirole</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-24 Hours of 7-hydroxy Ropinirole</measure>
    <time_frame>0-24 hours</time_frame>
    <description>Area under the plasma drug concentration-time curve of 7-hydroxy ropinirole</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in MDS-UPDRS Total Score</measure>
    <time_frame>Baseline and Weeks 4, 8 and 12</time_frame>
    <description>Efficacy of ropinirole implants presented as the mean change from baseline in MDS-UPDRS total score. Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Scale [MDS-UPDRS] is a questionnaire and examination rating motor and non-motor experiences, and motor complications. Score is summed to range from 0 to 272. Higher score indicates more severe symptoms/outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline of Awake Time &quot;On&quot;</measure>
    <time_frame>Baseline and Weeks 1, 2, 3, 4, 6, 8, 10, 12</time_frame>
    <description>Efficacy of ropinirole implants presented as mean change from baseline of awake time &quot;on&quot;. Diaries were completed for 2 consecutive days prior to the visit, used to record motor state in half-hour intervals over a 24-hour period (during waking hours). &quot;On&quot; refers to when medication is providing benefit with regard to mobility, slowness and stiffness, regardless of dyskinesia. Daily totals for waking hours were normalized to a 16-hour waking day and averaged across the 2 days.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline of Awake Time &quot;Off&quot;</measure>
    <time_frame>Baseline and Weeks 1, 2, 3, 4, 6, 8, 10, 12</time_frame>
    <description>Efficacy of ropinirole implants presented as mean change from baseline of awake time &quot;Off&quot;. Diaries were completed for 2 consecutive days prior to the visit, used to record motor state in half-hour intervals over a 24-hour period (during waking hours). &quot;Off&quot; refers to when medication has worn off and is no longer providing benefit with regard to mobility, slowness and stiffness. Daily totals for waking hours were normalized to a 16-hour waking day and averaged across the 2 days</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Parkinson Disease</condition>
  <arm_group>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Requip; One Ropinirole Implant</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Requip; Two Ropinirole Implants</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Requip; Three Ropinirole Implants</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Requip; Four Ropinirole Implants</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ropinirole oral product</intervention_name>
    <description>oral immediate-release ropinirole</description>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_label>Cohort 4</arm_group_label>
    <other_name>Requip</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ropinirole Implant</intervention_name>
    <description>ropinirole hydrochloride/ethylene vinyl acetate</description>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_label>Cohort 4</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Voluntarily provided informed consent&#xD;
&#xD;
          -  Meet diagnostic criteria for idiopathic Parkinson's Disease&#xD;
&#xD;
          -  On L-Dopa and oral ropinirole&#xD;
&#xD;
          -  If female of child-bearing potential, willing to practice contraception from time of&#xD;
             informed consent to Follow-Up Visit&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant, breastfeeding, or planning to become pregnant&#xD;
&#xD;
          -  Active epilepsy within the past year&#xD;
&#xD;
          -  Severe dementia or cognitive impairment&#xD;
&#xD;
          -  Donated or lost &gt; 400 mL of blood within 1 month prior to Screening&#xD;
&#xD;
          -  History of alcohol or substance use disorder within the prior 12 months&#xD;
&#xD;
          -  Recent episodes of moderate to severe dizziness or syncope&#xD;
&#xD;
          -  Definite or suspected hypersensitivity to ropinirole or ethylene vinyl acetate&#xD;
&#xD;
          -  Used any other investigational drug within 60 days or 5 half-lives prior to Screening,&#xD;
             or plan to take any such drug any time during the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dr. Kate Beebe DeVarney</last_name>
    <role>Study Director</role>
    <affiliation>Titan Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Orlando, Florida</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Farmington Hills, Michigan</name>
      <address>
        <city>Farmington Hills</city>
        <state>Michigan</state>
        <zip>48334</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kirkland, Washington</name>
      <address>
        <city>Kirkland</city>
        <state>Washington</state>
        <zip>98034</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>August 11, 2017</study_first_submitted>
  <study_first_submitted_qc>August 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <results_first_submitted>February 28, 2023</results_first_submitted>
  <results_first_submitted_qc>April 10, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">May 6, 2023</results_first_posted>
  <disposition_first_submitted>January 23, 2020</disposition_first_submitted>
  <disposition_first_submitted_qc>April 10, 2023</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">May 6, 2023</disposition_first_posted>
  <last_update_submitted>April 10, 2023</last_update_submitted>
  <last_update_submitted_qc>April 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Parkinson Disease</keyword>
  <keyword>Dyskinesia</keyword>
  <keyword>ropinirole</keyword>
  <keyword>implant</keyword>
  <keyword>ProNeura</keyword>
  <keyword>movement disorders</keyword>
  <keyword>dopamine agonist</keyword>
  <keyword>extended-release</keyword>
  <keyword>Parkinsonian disorders</keyword>
  <keyword>brain diseases</keyword>
  <keyword>central nervous system diseases</keyword>
  <keyword>Neurodegenerative Diseases</keyword>
  <keyword>Antiparkinson agents</keyword>
  <keyword>Anti-dyskinesia agents</keyword>
  <keyword>dopamine agents</keyword>
  <keyword>neurotransmitter agents</keyword>
  <keyword>REQUIP</keyword>
  <keyword>subdermal</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>Ropinirole</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <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>June 7, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/17/NCT03250117/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>May 11, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/17/NCT03250117/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Of 6 screened patients, 3 did not meet eligibility criteria for cohort assignment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Cohort 1</title>
          <description>Requip; One Ropinirole Implant</description>
        </group>
        <group group_id="P2">
          <title>Cohort 2</title>
          <description>Requip; Two Ropinirole Implants</description>
        </group>
        <group group_id="P3">
          <title>Cohort 3</title>
          <description>Requip; Three Ropinirole Implants</description>
        </group>
        <group group_id="P4">
          <title>Cohort 4</title>
          <description>Requip; Four Ropinirole Implants</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Requip IR [7-10 Days]</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0">Study terminated before cohort opened to enrollment</participants>
                <participants group_id="P3" count="0">Study terminated before cohort opened to enrollment</participants>
                <participants group_id="P4" count="0">Study terminated before cohort opened to enrollment</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Ropinirole Implant 12 Weeks</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>At request of Sponsor, regulatory agencies, or the IRB</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Cohort 1</title>
          <description>Requip; One Ropinirole Implant</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="3"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="52.7" lower_limit="47" upper_limit="58"/>
                  </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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </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="1"/>
                  </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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </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>MDS-UPDRS Total Score</title>
          <description>Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Scale [MDS-UPDRS] is a questionnaire and examination rating motor and non-motor experiences, and motor complications. Score is summed to range from 0 to 272. Higher score indicates more severe symptoms/outcome.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="60.7" lower_limit="23" upper_limit="97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Awake Time &quot;On&quot;</title>
          <description>Diaries were completed for 2 consecutive days prior to the visit, used to record motor state in half-hour intervals over a 24-hour period (during waking hours). &quot;On&quot; refers to when medication is providing benefit with regard to mobility, slowness and stiffness, regardless of dyskinesia. Daily totals for waking hours were normalized to a 16-hour waking day and averaged across the 2 days.</description>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11.54" lower_limit="9.9" upper_limit="14.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Awake Time &quot;Off&quot;</title>
          <description>Diaries were completed for 2 consecutive days prior to the visit, used to record motor state in half-hour intervals over a 24-hour period (during waking hours). &quot;Off&quot; refers to when medication has worn off and is no longer providing benefit with regard to mobility, slowness and stiffness. Daily totals for waking hours were normalized to a 16-hour waking day and averaged across the 2 days.</description>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5.02" lower_limit="3.4" upper_limit="6.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>AUC0-24 Hours of Ropinirole</title>
        <description>Area under the plasma drug concentration-time curve of ropinirole</description>
        <time_frame>0-24 hours</time_frame>
        <population>Subjects who received at least 1 ropinirole implant and for whom at least 1 PK parameter of interest can be calculated were to be included in this analysis. Analysis not performed due to insufficient representative samples from each cohort.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1</title>
            <description>Requip; One Ropinirole Implant</description>
          </group>
        </group_list>
        <measure>
          <title>AUC0-24 Hours of Ropinirole</title>
          <description>Area under the plasma drug concentration-time curve of ropinirole</description>
          <population>Subjects who received at least 1 ropinirole implant and for whom at least 1 PK parameter of interest can be calculated were to be included in this analysis. Analysis not performed due to insufficient representative samples from each cohort.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Total Number of Adverse Events Across Participants</title>
        <description>Safety and tolerability of ropinirole implant(s) presented as the total number of adverse events experienced by the analysis population.</description>
        <time_frame>0-12 weeks</time_frame>
        <population>Subjects who received a least 1 ropinirole implant</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1</title>
            <description>Requip; One Ropinirole Implant</description>
          </group>
        </group_list>
        <measure>
          <title>Total Number of Adverse Events Across Participants</title>
          <description>Safety and tolerability of ropinirole implant(s) presented as the total number of adverse events experienced by the analysis population.</description>
          <population>Subjects who received a least 1 ropinirole implant</population>
          <units>Events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC0-24 Hours of N-despropyl Ropinirole</title>
        <description>Area under the plasma drug concentration-time curve of N-despropyl ropinirole</description>
        <time_frame>0-24 hours</time_frame>
        <population>Subjects who received at least 1 ropinirole implant and for whom at least 1 PK parameter of interest can be calculated were to be included in this analysis. Analysis not performed due to insufficient representative samples from each cohort.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1</title>
            <description>Requip; One Ropinirole Implant</description>
          </group>
        </group_list>
        <measure>
          <title>AUC0-24 Hours of N-despropyl Ropinirole</title>
          <description>Area under the plasma drug concentration-time curve of N-despropyl ropinirole</description>
          <population>Subjects who received at least 1 ropinirole implant and for whom at least 1 PK parameter of interest can be calculated were to be included in this analysis. Analysis not performed due to insufficient representative samples from each cohort.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC0-24 Hours of 7-hydroxy Ropinirole</title>
        <description>Area under the plasma drug concentration-time curve of 7-hydroxy ropinirole</description>
        <time_frame>0-24 hours</time_frame>
        <population>Subjects who received at least 1 ropinirole implant and for whom at least 1 PK parameter of interest can be calculated were to be included in this analysis. Analysis not performed due to insufficient representative samples from each cohort.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1</title>
            <description>Requip; One Ropinirole Implant</description>
          </group>
        </group_list>
        <measure>
          <title>AUC0-24 Hours of 7-hydroxy Ropinirole</title>
          <description>Area under the plasma drug concentration-time curve of 7-hydroxy ropinirole</description>
          <population>Subjects who received at least 1 ropinirole implant and for whom at least 1 PK parameter of interest can be calculated were to be included in this analysis. Analysis not performed due to insufficient representative samples from each cohort.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in MDS-UPDRS Total Score</title>
        <description>Efficacy of ropinirole implants presented as the mean change from baseline in MDS-UPDRS total score. Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Scale [MDS-UPDRS] is a questionnaire and examination rating motor and non-motor experiences, and motor complications. Score is summed to range from 0 to 272. Higher score indicates more severe symptoms/outcome.</description>
        <time_frame>Baseline and Weeks 4, 8 and 12</time_frame>
        <population>Subjects who receive at least 1 ropinirole implant and complete at least 1 post-baseline efficacy assessment. Three subjects were in the analysis population at Week 4. Two subjects were in the analysis population at Weeks 8 and 12.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1</title>
            <description>Requip; One Ropinirole Implant</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in MDS-UPDRS Total Score</title>
          <description>Efficacy of ropinirole implants presented as the mean change from baseline in MDS-UPDRS total score. Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Scale [MDS-UPDRS] is a questionnaire and examination rating motor and non-motor experiences, and motor complications. Score is summed to range from 0 to 272. Higher score indicates more severe symptoms/outcome.</description>
          <population>Subjects who receive at least 1 ropinirole implant and complete at least 1 post-baseline efficacy assessment. Three subjects were in the analysis population at Week 4. Two subjects were in the analysis population at Weeks 8 and 12.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.0" spread="3.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.6" spread="13.42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.3" spread="4.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline of Awake Time &quot;On&quot;</title>
        <description>Efficacy of ropinirole implants presented as mean change from baseline of awake time &quot;on&quot;. Diaries were completed for 2 consecutive days prior to the visit, used to record motor state in half-hour intervals over a 24-hour period (during waking hours). &quot;On&quot; refers to when medication is providing benefit with regard to mobility, slowness and stiffness, regardless of dyskinesia. Daily totals for waking hours were normalized to a 16-hour waking day and averaged across the 2 days.</description>
        <time_frame>Baseline and Weeks 1, 2, 3, 4, 6, 8, 10, 12</time_frame>
        <population>Subjects who receive at least 1 ropinirole implant and complete at least 1 post-baseline efficacy assessment. Three subjects were in the analysis population for Weeks 1-6. Two subjects were in the analysis population for Weeks 8-12.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1</title>
            <description>Requip; One Ropinirole Implant</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline of Awake Time &quot;On&quot;</title>
          <description>Efficacy of ropinirole implants presented as mean change from baseline of awake time &quot;on&quot;. Diaries were completed for 2 consecutive days prior to the visit, used to record motor state in half-hour intervals over a 24-hour period (during waking hours). &quot;On&quot; refers to when medication is providing benefit with regard to mobility, slowness and stiffness, regardless of dyskinesia. Daily totals for waking hours were normalized to a 16-hour waking day and averaged across the 2 days.</description>
          <population>Subjects who receive at least 1 ropinirole implant and complete at least 1 post-baseline efficacy assessment. Three subjects were in the analysis population for Weeks 1-6. Two subjects were in the analysis population for Weeks 8-12.</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.80" spread="1.078"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.11" spread="0.457"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.70" spread="0.908"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.77" spread="0.608"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.66" spread="1.175"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.11" spread="1.344"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.93" spread="0.756"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.58" spread="1.101"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline of Awake Time &quot;Off&quot;</title>
        <description>Efficacy of ropinirole implants presented as mean change from baseline of awake time &quot;Off&quot;. Diaries were completed for 2 consecutive days prior to the visit, used to record motor state in half-hour intervals over a 24-hour period (during waking hours). &quot;Off&quot; refers to when medication has worn off and is no longer providing benefit with regard to mobility, slowness and stiffness. Daily totals for waking hours were normalized to a 16-hour waking day and averaged across the 2 days</description>
        <time_frame>Baseline and Weeks 1, 2, 3, 4, 6, 8, 10, 12</time_frame>
        <population>Subjects who receive at least 1 ropinirole implant and complete at least 1 post-baseline efficacy assessment. Three subjects were in the analysis population for Weeks 1-6. Two subjects were in the analysis population for Weeks 8-12.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1</title>
            <description>Requip; One Ropinirole Implant</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline of Awake Time &quot;Off&quot;</title>
          <description>Efficacy of ropinirole implants presented as mean change from baseline of awake time &quot;Off&quot;. Diaries were completed for 2 consecutive days prior to the visit, used to record motor state in half-hour intervals over a 24-hour period (during waking hours). &quot;Off&quot; refers to when medication has worn off and is no longer providing benefit with regard to mobility, slowness and stiffness. Daily totals for waking hours were normalized to a 16-hour waking day and averaged across the 2 days</description>
          <population>Subjects who receive at least 1 ropinirole implant and complete at least 1 post-baseline efficacy assessment. Three subjects were in the analysis population for Weeks 1-6. Two subjects were in the analysis population for Weeks 8-12.</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.36" spread="0.974"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.67" spread="0.921"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.26" spread="1.062"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.33" spread="1.094"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.22" spread="1.506"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.83" spread="2.068"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.77" spread="1.598"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.43" spread="1.943"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From signing of the ICF until 30 days following study drug treatment discontinuation, up to 22 weeks.</time_frame>
      <desc>Subjects assessed for AEs at every visit, routine collection of safety labs, and spontaneous self-reporting.</desc>
      <group_list>
        <group group_id="E1">
          <title>Cohort 1</title>
          <description>Requip; One Ropinirole Implant</description>
        </group>
      </group_list>
      <serious_events>
        <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="3"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (20.0)</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="2" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Implant site reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Freezing phenomenon</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Affect lability</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hallucination, visual</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The Sponsor has rights to first publication of results unless waived by Sponsor. PIs may publish following Sponsor first publication or 18 months after conclusion, abandonment or termination of study. Sponsor to review proposed publications prior to public release and can embargo results for up to 60 days from the time submitted to the Sponsor for review and may remove any information that is considered confidential and/or proprietary other than Study data and results.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>This was a first-in-human study of ropinirole implants. The trial was terminated early at the request of the Sponsor, not for reasons of safety or efficacy.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Kate Beebe DeVarney, PhD</name_or_title>
      <organization>Titan Pharmaceuticals, Inc.</organization>
      <phone>650-244-4990</phone>
      <email>medinfo@titanpharm.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/NCT03250117
org study id: ROP-001
nct id: NCT03250117
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Subjects stable on L-Dopa and oral ropinirole will have their ropinirole replaced with the
      Ropinirole Implant(s). The Ropinirole Implant was designed using the ProNeura™ implant
      technology where the implant is inserted under the skin. This study will measure how much
      ropinirole is released in the blood during 12 weeks of ropinirole implant treatment, and
      evaluate the side effects of this new formulation.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: Subjects receive oral immediate release (IR) ropinirole for 7-10 days, and then are switched to ropinirole implant(s) for 12 weeks.
primary purpose: Treatment
masking: None (Open Label)
measure: AUC0-24 Hours of Ropinirole
time frame: 0-24 hours
description: Area under the plasma drug concentration-time curve of ropinirole
measure: Total Number of Adverse Events Across Participants
time frame: 0-12 weeks
description: Safety and tolerability of ropinirole implant(s) presented as the total number of adverse events experienced by the analysis population.
measure: AUC0-24 Hours of N-despropyl Ropinirole
time frame: 0-24 hours
description: Area under the plasma drug concentration-time curve of N-despropyl ropinirole
measure: AUC0-24 Hours of 7-hydroxy Ropinirole
time frame: 0-24 hours
description: Area under the plasma drug concentration-time curve of 7-hydroxy ropinirole
measure: Mean Change From Baseline in MDS-UPDRS Total Score
time frame: Baseline and Weeks 4, 8 and 12
description: Efficacy of ropinirole implants presented as the mean change from baseline in MDS-UPDRS total score. Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Scale [MDS-UPDRS] is a questionnaire and examination rating motor and non-motor experiences, and motor complications. Score is summed to range from 0 to 272. Higher score indicates more severe symptoms/outcome.
measure: Mean Change From Baseline of Awake Time "On"
time frame: Baseline and Weeks 1, 2, 3, 4, 6, 8, 10, 12
description: Efficacy of ropinirole implants presented as mean change from baseline of awake time "on". Diaries were completed for 2 consecutive days prior to the visit, used to record motor state in half-hour intervals over a 24-hour period (during waking hours). "On" refers to when medication is providing benefit with regard to mobility, slowness and stiffness, regardless of dyskinesia. Daily totals for waking hours were normalized to a 16-hour waking day and averaged across the 2 days.
measure: Mean Change From Baseline of Awake Time "Off"
time frame: Baseline and Weeks 1, 2, 3, 4, 6, 8, 10, 12
description: Efficacy of ropinirole implants presented as mean change from baseline of awake time "Off". Diaries were completed for 2 consecutive days prior to the visit, used to record motor state in half-hour intervals over a 24-hour period (during waking hours). "Off" refers to when medication has worn off and is no longer providing benefit with regard to mobility, slowness and stiffness. Daily totals for waking hours were normalized to a 16-hour waking day and averaged across the 2 days
arm group label: Cohort 1
arm group type: Experimental
description: Requip; One Ropinirole Implant
arm group label: Cohort 2
arm group type: Experimental
description: Requip; Two Ropinirole Implants
arm group label: Cohort 3
arm group type: Experimental
description: Requip; Three Ropinirole Implants
arm group label: Cohort 4
arm group type: Experimental
description: Requip; Four Ropinirole Implants
intervention type: Drug
intervention name: Ropinirole oral product
description: oral immediate-release ropinirole
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3
arm group label: Cohort 4
other name: Requip
intervention type: Drug
intervention name: Ropinirole Implant
description: ropinirole hydrochloride/ethylene vinyl acetate
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3
arm group label: Cohort 4
criteria: 
gender: All
minimum age: 30 Years
maximum age: 80 Years
healthy volunteers: No
last name: Dr. Kate Beebe DeVarney
role: Study Director
affiliation: Titan Pharmaceuticals
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Parkinson Disease
mesh term: Ropinirole
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: This was a first-in-human study of ropinirole implants. The trial was terminated early at the request of the Sponsor, not for reasons of safety or efficacy.
point of contact: 