<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/NCT03038308</url>
  </required_header>
  <id_info>
    <org_study_id>AAAI8604</org_study_id>
    <secondary_id>1R21DK112093-01</secondary_id>
    <nct_id>NCT03038308</nct_id>
  </id_info>
  <brief_title>Treatment of Hyperprolactinemia With the Non-ergoline Dopamine Agonist Ropinirole</brief_title>
  <official_title>Treatment of Hyperprolactinemia With the Non-ergoline Dopamine Agonist Ropinirole: A Dose Escalation Study of Efficacy and Tolerability</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Columbia University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Columbia University</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the use of the non-ergoline dopamine agonist&#xD;
      ropinirole for the treatment of hyperprolactinemia in patients with idiopathic&#xD;
      hyperprolactinemia and prolactinomas.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Treatment of prolactin secreting pituitary tumors with traditional ergot dopamine agonist&#xD;
      drugs can be limited by medication side effects, pharmacologic resistance, and by concerns&#xD;
      regarding the potential risk of cardiac valve disease. The overall goal of this project is&#xD;
      therefore to evaluate, for the first time, the efficacy and tolerability of the selective&#xD;
      D2/D3 receptor non-ergot dopamine agonist ropinirole for the treatment of prolactinomas. This&#xD;
      proposal will establish the pharmacologic profile of this medication when used to treat&#xD;
      hyperprolactinemia in patients with prolactinomas and will determine the impact of long-term&#xD;
      ropinirole administration on critical clinical parameters including serum prolactin levels,&#xD;
      gonadal function, and tumor regression, in order to establish ropinirole's utility as a new,&#xD;
      clinically efficacious, safer and more tolerable therapeutic option for the treatment of&#xD;
      prolactinomas that may prove particularly useful in patients with underlying cardiac valve&#xD;
      disease and in those with resistance or intolerance to ergot dopamine agonists.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 16, 2016</start_date>
  <completion_date type="Actual">November 5, 2020</completion_date>
  <primary_completion_date type="Actual">November 5, 2020</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>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>1) Forced titration dose response PKPD study and 2) A prospective open-label outpatient dose escalation trial of ropinirole for treatment of prolactinomas and hyperprolactinemia.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Open-label studies</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Subjects That Achieved Stable PRL Normalization</measure>
    <time_frame>6-12 months</time_frame>
    <description>Serum prolactin concentrations (PRL levels) were measured in patients at baseline and at follow-up.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Subjects With Unchanged Tumor Size</measure>
    <time_frame>6-12 months</time_frame>
    <description>Radiologic assessment of tumor size before and after treatment will be made by MRI.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Hyperprolactinemia</condition>
  <condition>Prolactinoma</condition>
  <arm_group>
    <arm_group_label>ROP Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with hyperprolactinemia were treated with long-term ROP therapy for 6 months in an open-label dose escalation study</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ropinirole</intervention_name>
    <description>0.25mg/day - 6.0mg/day oral non-ergoline dopamine agonist ropinirole</description>
    <arm_group_label>ROP Intervention</arm_group_label>
    <other_name>ROP therapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ages 18-70 years&#xD;
&#xD;
          -  Prolactin level (PRL) ≥2 times upper limit of normal&#xD;
&#xD;
          -  Pituitary adenomas on MRI ≤ 1.5cm in greatest diameter and ≥ 5mm from the optic chiasm&#xD;
&#xD;
          -  Normal renal and liver function&#xD;
&#xD;
          -  Agrees to barrier contraception if pre-menopausal&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Use of medications known to interfere with PRL secretion and PRL and Ropinirole (ROP)&#xD;
             metabolism&#xD;
&#xD;
          -  Use of another dopamine agonist during the 4 weeks prior&#xD;
&#xD;
          -  Pituitary stalk compression on MRI&#xD;
&#xD;
          -  History of visual field abnormalities or previous radiation&#xD;
&#xD;
          -  Untreated hypothyroidism&#xD;
&#xD;
          -  Consumption of &gt; 2 alcoholic drinks per day&#xD;
&#xD;
          -  Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gabrielle Page-Wilson, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Columbia University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Liu S, Hu C, Peters J, Tsang A, Cremers S, Bies R, Page-Wilson G. Pharmacokinetics and pharmacodynamics of ropinirole in patients with prolactinomas. Br J Clin Pharmacol. 2019 Feb;85(2):366-376. doi: 10.1111/bcp.13802. Epub 2018 Nov 22.</citation>
    <PMID>30362146</PMID>
  </reference>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>January 30, 2017</study_first_submitted>
  <study_first_submitted_qc>January 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 31, 2017</study_first_posted>
  <results_first_submitted>July 9, 2021</results_first_submitted>
  <results_first_submitted_qc>July 9, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">July 30, 2021</results_first_posted>
  <last_update_submitted>July 9, 2021</last_update_submitted>
  <last_update_submitted_qc>July 9, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 30, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ropinirole</keyword>
  <keyword>hyperprolactinemia</keyword>
  <keyword>prolactin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prolactinoma</mesh_term>
    <mesh_term>Hyperprolactinemia</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 and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 5, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/08/NCT03038308/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>1 Subject was determined to be ineligible after consenting.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>ROP Intervention</title>
          <description>Patients with hyperprolactinemia were treated with long-term ROP therapy for 6 months in an open-label dose escalation study&#xD;
Ropinirole: 0.25mg/day - 6.0mg/day oral non-ergoline dopamine agonist ropinirole</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Only 15 out of 16 enrolled subjects went on to receive study therapy; however, demographic information was collected for all 16 enrolled subjects.</population>
      <group_list>
        <group group_id="B1">
          <title>ROP Intervention</title>
          <description>Patients with hyperprolactinemia were treated with long-term ROP therapy for 6 months in an open-label dose escalation study&#xD;
Ropinirole: 0.25mg/day - 6.0mg/day oral non-ergoline dopamine agonist ropinirole</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="16"/>
          </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="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </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="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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="13"/>
                  </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="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </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>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Subjects That Achieved Stable PRL Normalization</title>
        <description>Serum prolactin concentrations (PRL levels) were measured in patients at baseline and at follow-up.</description>
        <time_frame>6-12 months</time_frame>
        <population>Data for 10 out of 11 completers were included in this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>ROP Intervention</title>
            <description>Patients with hyperprolactinemia were treated with long-term ROP therapy for 6 months in an open-label dose escalation study&#xD;
Ropinirole: 0.25mg/day - 6.0mg/day oral non-ergoline dopamine agonist ropinirole</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects That Achieved Stable PRL Normalization</title>
          <description>Serum prolactin concentrations (PRL levels) were measured in patients at baseline and at follow-up.</description>
          <population>Data for 10 out of 11 completers were included in this analysis.</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="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Subjects With Unchanged Tumor Size</title>
        <description>Radiologic assessment of tumor size before and after treatment will be made by MRI.</description>
        <time_frame>6-12 months</time_frame>
        <population>Data for 8 out of 11 completers with prolactinomas were included in this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>ROP Intervention</title>
            <description>Patients with hyperprolactinemia were treated with long-term ROP therapy for 6 months in an open-label dose escalation study&#xD;
Ropinirole: 0.25mg/day - 6.0mg/day oral non-ergoline dopamine agonist ropinirole</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects With Unchanged Tumor Size</title>
          <description>Radiologic assessment of tumor size before and after treatment will be made by MRI.</description>
          <population>Data for 8 out of 11 completers with prolactinomas were included in this analysis.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>6 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>ROP Intervention</title>
          <description>Patients with hyperprolactinemia were treated with long-term ROP therapy for 6 months in an open-label dose escalation study&#xD;
Ropinirole: 0.25mg/day - 6.0mg/day oral non-ergoline dopamine agonist ropinirole</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="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Non-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="8" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Gabrielle Page-Wilson, MD</name_or_title>
      <organization>Columbia University</organization>
      <phone>212-305-3725</phone>
      <email>gp2287@cumc.columbia.edu</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/NCT03038308
org study id: AAAI8604
secondary id: 1R21DK112093-01
nct id: NCT03038308
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this study is to evaluate the use of the non-ergoline dopamine agonist
      ropinirole for the treatment of hyperprolactinemia in patients with idiopathic
      hyperprolactinemia and prolactinomas.
Treatment of prolactin secreting pituitary tumors with traditional ergot dopamine agonist
      drugs can be limited by medication side effects, pharmacologic resistance, and by concerns
      regarding the potential risk of cardiac valve disease. The overall goal of this project is
      therefore to evaluate, for the first time, the efficacy and tolerability of the selective
      D2/D3 receptor non-ergot dopamine agonist ropinirole for the treatment of prolactinomas. This
      proposal will establish the pharmacologic profile of this medication when used to treat
      hyperprolactinemia in patients with prolactinomas and will determine the impact of long-term
      ropinirole administration on critical clinical parameters including serum prolactin levels,
      gonadal function, and tumor regression, in order to establish ropinirole's utility as a new,
      clinically efficacious, safer and more tolerable therapeutic option for the treatment of
      prolactinomas that may prove particularly useful in patients with underlying cardiac valve
      disease and in those with resistance or intolerance to ergot dopamine agonists.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: 1) Forced titration dose response PKPD study and 2) A prospective open-label outpatient dose escalation trial of ropinirole for treatment of prolactinomas and hyperprolactinemia.
primary purpose: Treatment
masking: None (Open Label)
masking description: Open-label studies
measure: Percentage of Subjects That Achieved Stable PRL Normalization
time frame: 6-12 months
description: Serum prolactin concentrations (PRL levels) were measured in patients at baseline and at follow-up.
measure: Number of Subjects With Unchanged Tumor Size
time frame: 6-12 months
description: Radiologic assessment of tumor size before and after treatment will be made by MRI.
arm group label: ROP Intervention
arm group type: Experimental
description: Patients with hyperprolactinemia were treated with long-term ROP therapy for 6 months in an open-label dose escalation study
intervention type: Drug
intervention name: Ropinirole
description: 0.25mg/day - 6.0mg/day oral non-ergoline dopamine agonist ropinirole
arm group label: ROP Intervention
other name: ROP therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Gabrielle Page-Wilson, M.D.
role: Principal Investigator
affiliation: Columbia University
facility: 
country: United States
citation: Liu S, Hu C, Peters J, Tsang A, Cremers S, Bies R, Page-Wilson G. Pharmacokinetics and pharmacodynamics of ropinirole in patients with prolactinomas. Br J Clin Pharmacol. 2019 Feb;85(2):366-376. doi: 10.1111/bcp.13802. Epub 2018 Nov 22.
PMID: 30362146
responsible party type: Sponsor
mesh term: Prolactinoma
mesh term: Hyperprolactinemia
mesh term: Ropinirole
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 