xml: <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/NCT05971758</url>
    </required_header>
    <id_info>
      <org_study_id>FD-07548-01-A1</org_study_id>
      <nct_id>NCT05971758</nct_id>
    </id_info>
    <brief_title>Fimepinostat, Combination HDAC and Pi3-kinase Inhibitor Tumor-Directed Therapy for Cushing Disease</brief_title>
    <official_title>Fimepinostat, Combination HDAC and Pi3-kinase Inhibitor Tumor-Directed Therapy for Cushing Disease</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of California, Los Angeles</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of California, Los Angeles</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>
        Supported by the pre-clinical data (summarized in Research Strategy), the investigators&#xD;
        propose that Fimepinostat is an ideal candidate drug in the treatment and intervention of&#xD;
        patients with Cushing Disease. The investigators propose a pilot, short-term (4 weeks) phase&#xD;
        II single-center study to demonstrate the safety and efficacy of Fimepinostat in the&#xD;
        treatment of patients with de novo, persistent, and/or recurrent CD recruited at the&#xD;
        University of California, Los Angeles. The trial will have a 2-arm design and will&#xD;
        simultaneously examine two different doses of Fimepinostat. The study will allow the&#xD;
        investigators to determine the efficacy and safety of these doses in the treatment of CD and&#xD;
        guide dose selection for subsequent, larger studies.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">January 2024</start_date>
    <completion_date type="Anticipated">January 2025</completion_date>
    <primary_completion_date type="Anticipated">January 2025</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Number of participants with mUFC ≤ 1.0xULN</measure>
      <time_frame>Baseline, 4 weeks</time_frame>
      <description>4 week UFC calculated as the mean of three 24h UFC specimens collected on consecutive days between day 24-28</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Number of participants with normalization (values within normal limits) or &gt;50% improvement from baseline in 24h UFC, plasma ACTH, serum and salivary cortisol levels</measure>
      <time_frame>Baseline, 4 weeks</time_frame>
      <description>4 week UFC calculated as the mean of three 24h UFC specimens collected on consecutive days between day 24-28</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>body weight change from baseline</measure>
      <time_frame>Baseline, Day 28</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>body mass index change from baseline</measure>
      <time_frame>Baseline, Day 28</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Systolic and Diastolic Blood Pressure Change from baseline</measure>
      <time_frame>Baseline, Day 28</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cushing Disease health-related quality of life questionnaire (CushingQoL) change from baseline</measure>
      <time_frame>Baseline, Day 28</time_frame>
      <description>The CushingQoL is scored using a total score ranging from 0 to 100 with lower scores indicating a greater impact on QoL</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Beck Depression inventory second edition (BDIII) change from baseline</measure>
      <time_frame>Baseline, Day 28</time_frame>
      <description>Beck Depression scale is scored as follows 1-10 These ups and downs are considered normal. 11-16 Mild mood disturbances. 17-20 borderline clinical depression. 21-30 Moderate depression. 31-40 Severe depression</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">20</enrollment>
    <condition>Cushing Disease</condition>
    <arm_group>
      <arm_group_label>Fimepinostat 60mg</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>two 30mg capsules once a day, 10 subjects</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Fimepinostat 30mg</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>single 30mg capsule daily in 10 subjects</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Fimepinostat</intervention_name>
      <description>The study will allow us to determine the efficacy and safety of these doses in the treatment of Cushing Disease (CD) and guide dose selection for subsequent, larger studies.</description>
      <arm_group_label>Fimepinostat 30mg</arm_group_label>
      <arm_group_label>Fimepinostat 60mg</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Male and female patients at least 18 years old&#xD;
  &#xD;
            -  Patients with confirmed pituitary origin Cushing syndrome defined as 1, 2&amp; 3 or 4 &amp; 5&#xD;
               below:&#xD;
  &#xD;
                 1. Persistent hypercortisolism defined as a mean of 3 consecutive 24h UFC at&#xD;
                    baseline assessment ≥ 1.3x ULN&#xD;
  &#xD;
                 2. Normal or elevated plasma ACTH levels&#xD;
  &#xD;
                 3. Pituitary adenoma &gt; 4mm visible on MRI or inferior petrosal sinus sampling (IPSS)&#xD;
                    central to peripheral ACTH gradient &gt;2 at baseline and/or &gt;2 after DDAVP&#xD;
                    stimulation.&#xD;
  &#xD;
                 4. Recurrent or persistent CD defined as pathologically confirmed previously&#xD;
                    resected pituitary ACTH-secreting tumor, and 24 hour UFC &gt;ULN at least 4 weeks&#xD;
                    after pituitary surgery.&#xD;
  &#xD;
                 5. Patients on medical treatment for CD. Washout periods will be completed as below&#xD;
                    before screening: Inhibitors of steroidogenesis (metyrapone, ketoconazole,&#xD;
                    osilodristat,&#xD;
  &#xD;
                      -  Levo-ketoconazole): 2 weeks&#xD;
  &#xD;
                      -  SRLs (pasireotide): 2 weeks&#xD;
  &#xD;
                      -  Progesterone receptor antagonist (mifepristone): 2 weeks&#xD;
  &#xD;
                      -  Dopamine agonists (cabergoline): 4 weeks&#xD;
  &#xD;
                      -  CYP3A4 strong inducers or inhibitors: varies between drugs; minimum 5-6&#xD;
                         times the half-life of drug&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients with compromised visual fields, or evidence of visual changes within past 6&#xD;
               months&#xD;
  &#xD;
            -  Patients with sellar tumor abutting or compressing the optic chiasm on MRI and normal&#xD;
               visual fields&#xD;
  &#xD;
            -  Patients with Cushing's syndrome not due to an ACTH-secreting pituitary tumor&#xD;
  &#xD;
            -  Patients who have undergone major surgery including pituitary surgery within 1 month&#xD;
               of screening or who have any major surgical procedures planned across the study period&#xD;
  &#xD;
            -  Patients with serum potassium &lt; 3.5 mEq/L unless stably controlled on potassium&#xD;
               supplementation&#xD;
  &#xD;
            -  Patients with poorly-controlled Diabetes mellitus evidenced by HbA1c levels &gt;8&#xD;
  &#xD;
            -  Patients with poorly controlled hypertension (i.e. blood pressure ≥ 160/100 mm Hg)&#xD;
  &#xD;
            -  Patients who have clinically significant cardiovascular impairment, as evidenced by&#xD;
               the presence of bradycardia, ventricular tachycardia, history of myocardial infarction&#xD;
               within past year, or any other cardiovascular impairment that may pose significant&#xD;
               health risk in view of the investigator.&#xD;
  &#xD;
            -  Patients with liver disease or history of liver disease such as cirrhosis, chronic&#xD;
               active hepatitis B and C, or chronic persistent hepatitis, or patients with ALT or AST&#xD;
               &gt;1.5 x ULN, serum total bilirubin &gt;ULN, serum albumin &lt;0.67 x LLN at screening&#xD;
  &#xD;
            -  Patients with renal disease or history of renal disease with creatinine clearance of&#xD;
               30 cm3/min or less and/or creatinine &gt; 1.5 mg/dl at screening&#xD;
  &#xD;
            -  Patients not biochemically euthyroid. Patients receiving thyroid-replacement therapy&#xD;
               must be on a stable dose for at least 3 months.&#xD;
  &#xD;
            -  Patients who are known to be positive for HIV, or any other condition that&#xD;
               significantly compromises subject's immune system.&#xD;
  &#xD;
            -  History of alcohol abuse or illicit substance use within past year.&#xD;
  &#xD;
            -  Female patients who are pregnant or lactating or are of childbearing potential unless&#xD;
               willing to practice acceptable method of birth control. Women participating in the&#xD;
               trial must employ double barrier method through oral contraceptive or diaphragm with&#xD;
               partner utilizing a condom. Abstinence is an acceptable form of birth control if&#xD;
               routinely practiced. Male participants must utilize a condom with spermicidal&#xD;
               cap/jelly and agree to not donate sperm for up to 3 months beyond main study period.&#xD;
  &#xD;
            -  Patients who have participated in any clinical investigation with an investigational&#xD;
               drug within 1 month prior to screening or within 5 half-lives of the investigational&#xD;
               treatment whichever is longer.&#xD;
  &#xD;
            -  Patients with concomitant treatment of strong CYP3A4 inducers or inhibitors.&#xD;
  &#xD;
            -  Patients who have received pituitary irradiation within the last 5 years prior to the&#xD;
               baseline visit&#xD;
  &#xD;
            -  Patients with known hepatitis B surface antigen (HbsAg) positivity&#xD;
  &#xD;
            -  Patients with known hepatitis C antibody (anti-HCV) positivity&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 6, 2023</study_first_submitted>
    <study_first_submitted_qc>July 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 2, 2023</study_first_posted>
    <last_update_submitted>July 31, 2023</last_update_submitted>
    <last_update_submitted_qc>July 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 2, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of California, Los Angeles</investigator_affiliation>
      <investigator_full_name>Anthony P. Heaney</investigator_full_name>
      <investigator_title>Professor-in-Residence, Medicine</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>ACTH-Secreting Pituitary Adenoma</mesh_term>
      <mesh_term>Pituitary ACTH Hypersecretion</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05971758
  org study id: FD-07548-01-A1
  nct id: NCT05971758
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  Supported by the pre-clinical data (summarized in Research Strategy), the investigators
        propose that Fimepinostat is an ideal candidate drug in the treatment and intervention of
        patients with Cushing Disease. The investigators propose a pilot, short-term (4 weeks) phase
        II single-center study to demonstrate the safety and efficacy of Fimepinostat in the
        treatment of patients with de novo, persistent, and/or recurrent CD recruited at the
        University of California, Los Angeles. The trial will have a 2-arm design and will
        simultaneously examine two different doses of Fimepinostat. The study will allow the
        investigators to determine the efficacy and safety of these doses in the treatment of CD and
        guide dose selection for subsequent, larger studies.
  allocation: Randomized
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Number of participants with mUFC ≤ 1.0xULN
  time frame: Baseline, 4 weeks
  description: 4 week UFC calculated as the mean of three 24h UFC specimens collected on consecutive days between day 24-28
  measure: Number of participants with normalization (values within normal limits) or >50% improvement from baseline in 24h UFC, plasma ACTH, serum and salivary cortisol levels
  time frame: Baseline, 4 weeks
  description: 4 week UFC calculated as the mean of three 24h UFC specimens collected on consecutive days between day 24-28
  measure: body weight change from baseline
  time frame: Baseline, Day 28
  measure: body mass index change from baseline
  time frame: Baseline, Day 28
  measure: Systolic and Diastolic Blood Pressure Change from baseline
  time frame: Baseline, Day 28
  measure: Cushing Disease health-related quality of life questionnaire (CushingQoL) change from baseline
  time frame: Baseline, Day 28
  description: The CushingQoL is scored using a total score ranging from 0 to 100 with lower scores indicating a greater impact on QoL
  measure: Beck Depression inventory second edition (BDIII) change from baseline
  time frame: Baseline, Day 28
  description: Beck Depression scale is scored as follows 1-10 These ups and downs are considered normal. 11-16 Mild mood disturbances. 17-20 borderline clinical depression. 21-30 Moderate depression. 31-40 Severe depression
  arm group label: Fimepinostat 60mg
  arm group type: Active Comparator
  description: two 30mg capsules once a day, 10 subjects
  arm group label: Fimepinostat 30mg
  arm group type: Active Comparator
  description: single 30mg capsule daily in 10 subjects
  intervention type: Drug
  intervention name: Fimepinostat
  description: The study will allow us to determine the efficacy and safety of these doses in the treatment of Cushing Disease (CD) and guide dose selection for subsequent, larger studies.
  arm group label: Fimepinostat 30mg
  arm group label: Fimepinostat 60mg
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: Accepts Healthy Volunteers
  responsible party type: Principal Investigator
  investigator affiliation: University of California, Los Angeles
  investigator full name: Anthony P. Heaney
  investigator title: Professor-in-Residence, Medicine
  mesh term: ACTH-Secreting Pituitary Adenoma
  mesh term: Pituitary ACTH Hypersecretion