<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/NCT03282513</url>
  </required_header>
  <id_info>
    <org_study_id>AG120-C-012</org_study_id>
    <nct_id>NCT03282513</nct_id>
  </id_info>
  <brief_title>A Study of AG-120 (Ivosidenib) in Subjects With Mild or Moderate Hepatic Impairment or Normal Hepatic Function</brief_title>
  <official_title>A Phase 1, Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of AG-120 (Ivosidenib) in Subjects With Mild or Moderate Hepatic Impairment or Normal Hepatic Function</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Agios Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Agios Pharmaceuticals, Inc.</source>
  <oversight_info>
    <has_dmc>No</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>
      Study AG120-C-012 is a Phase 1, open-label, single-dose study designed to evaluate the PK,&#xD;
      safety, and tolerability of a single 500 mg AG-120 (Ivosidenib) dose in subjects with mild or&#xD;
      moderate hepatic impairment (HI) compared to subjects with normal hepatic function. The study&#xD;
      will be conducted at 2 US centers.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 26, 2017</start_date>
  <completion_date type="Actual">March 31, 2018</completion_date>
  <primary_completion_date type="Actual">March 31, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum observed plasma concentration (Cmax)</measure>
    <time_frame>Predose; 0.5hr, 1hr, 2hr, 3hr, 4hr, 6hr, 9hr, 12hr, 24hr, 48hr, 72hr, 120hr, 168hr, 240hr, 336hr, and 504hr post dose</time_frame>
    <description>AG-120 Cmax, derived from plasma concentration-time curves</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under plasma concentration-time curve (AUC)</measure>
    <time_frame>Predose; 0.5hr, 1hr, 2hr, 3hr, 4hr, 6hr, 9hr, 12hr, 24hr, 48hr, 72hr, 120hr, 168hr, 240hr, 336hr, and 504hr post dose</time_frame>
    <description>AG-120 AUC, derived from plasma concentration-time curves</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse Events (AE) and treatment-related AE</measure>
    <time_frame>From the time of study drug administration through the end of study (Day 29 or early termination)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Protein Binding</measure>
    <time_frame>Time Frame: Pre-dose, Day 1 and Day 2</time_frame>
    <description>Compare the plasma protein binding of AG-120 (Ivosidenib) in subjects with impaired HI with that in subjects with normal hepatic function.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">33</enrollment>
  <condition>Hepatic Impairment</condition>
  <arm_group>
    <arm_group_label>Cohort 1A: Mild Hepatic Impairment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug: AG-120 (Ivosidenib)&#xD;
A single 500 mg oral dose of AG-120 (Ivosidenib) in subjects with mild hepatic impairment(Child-Pugh Score A.)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 1B: Healthy Volunteers</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Drug: AG-120 (Ivosidenib)&#xD;
A single 500 mg oral dose of AG-120 (Ivosidenib) in subjects with normal hepatic function.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2A: Moderate Hepatic Impairment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug: AG-120 (Ivosidenib)&#xD;
A single 500 mg oral dose of AG-120 (Ivosidenib) in subjects with moderate hepatic impairment (Child-Pugh Score B.)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2B: Healthy Volunteers</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Drug: AG-120 (Ivosidenib)&#xD;
A single 500 mg oral dose of AG-120 (Ivosidenib) in subjects with normal hepatic function.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AG-120 (Ivosidenib)</intervention_name>
    <description>Single 500 mg dose of AG-120 (Ivosidenib).</description>
    <arm_group_label>Cohort 1A: Mild Hepatic Impairment</arm_group_label>
    <arm_group_label>Cohort 1B: Healthy Volunteers</arm_group_label>
    <arm_group_label>Cohort 2A: Moderate Hepatic Impairment</arm_group_label>
    <arm_group_label>Cohort 2B: Healthy Volunteers</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
        All subjects:&#xD;
&#xD;
          -  Body Mass Index BMI of 19 to 40 kg/m2 (inclusive).&#xD;
&#xD;
          -  Willing and able to comply with all study restrictions and requirements.&#xD;
&#xD;
          -  Non- smoker, or uses no more nicotine-containing product than the equivalent of&#xD;
             smoking ≤10 cigarettes per day, as judged by the investigator.&#xD;
&#xD;
          -  Female subjects must be non pregnant and non-lactating and either be post-menopausal,&#xD;
             surgically sterile, practice total abstinence from sexual intercourse as the preferred&#xD;
             lifestyle or agree to use an appropriate method of birth control consistently&#xD;
             throughout the study, from screening until 90 days after study drug administration.&#xD;
&#xD;
          -  Male subjects with a partner of child bearing potential must either be sterile,&#xD;
             practice total abstinence from sexual intercourse as the preferred life style or agree&#xD;
             to use an appropriate method of birth control consistently throughout the study, from&#xD;
             screening until 90 days after study drug administration.&#xD;
&#xD;
        Subjects with hepatic impairment (Cohorts 1a, 2a)&#xD;
&#xD;
          -  Diagnosis of chronic (≥3 months prior to Screening) or stable (no acute episodes of&#xD;
             illness within 2 months prior to Screening due to deterioration in hepatic function)&#xD;
             hepatic insufficiency, with a Child-Pugh classification score in the mild or moderate&#xD;
             range.&#xD;
&#xD;
          -  Hepatic insufficiency may be of any etiology associated with an unambiguous medical&#xD;
             history (such as evidence of portal hypertension).&#xD;
&#xD;
          -  Other than hepatic insufficiency with features of cirrhosis, subjects are in good&#xD;
             health based on medical history, physical exam, ECG, clinical laboratory tests, and&#xD;
             Investigator's assessment.&#xD;
&#xD;
        Healthy matched subjects (Cohorts 1b, 2b)&#xD;
&#xD;
        • Have normal hepatic function and considered by the Investigator to be in good health,&#xD;
        based on medical and surgical history review, physical exam, ECG, clinical laboratory&#xD;
        tests, and Investigator's assessment.&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
        All subjects:&#xD;
&#xD;
          -  Significant acute, new-onset illness (eg, flu, gastroenteritis) within 2 weeks prior&#xD;
             to dosing.&#xD;
&#xD;
          -  Positive test for drugs of abuse and/or positive alcohol test at Screening or prior to&#xD;
             dosing.&#xD;
&#xD;
          -  Medical history of clinically significant ECG abnormalities or a family history of&#xD;
             prolonged QT interval syndromes.&#xD;
&#xD;
          -  History of immunocompromise, including positivity for HIV, or active viral hepatitis B&#xD;
             or C.&#xD;
&#xD;
          -  Use of over the counter (OTC) medications, herbal supplements, grapefruit juice,&#xD;
             Seville oranges, or vitamins 14 days prior to dosing.&#xD;
&#xD;
          -  A recent (within 6 months prior to dosing) history of acute or chronic bronchospastic&#xD;
             disease, including asthma and chronic obstructive pulmonary disease.&#xD;
&#xD;
          -  Current or history of hepatic carcinoma, hepatorenal syndrome, portacaval shunt&#xD;
             surgery, or pleural effusion. Malignancy, including leukemia and lymphoma, within the&#xD;
             last 5 years.&#xD;
&#xD;
          -  Any surgical or medical condition that might significantly alter the absorption,&#xD;
             distribution, or excretion of AG-120.&#xD;
&#xD;
          -  Treatment with strong cytochrome P450 (CYP)3A4 inhibitors or inducers within 14 days&#xD;
             prior to AG 120 dosing or during the study.&#xD;
&#xD;
        Subjects with hepatic impairment (Cohorts 1a, 2a)&#xD;
&#xD;
          -  Clinical evidence of moderate to severe ascites.&#xD;
&#xD;
          -  Significant history or clinical manifestation of any significant metabolic/endocrine,&#xD;
             allergic, dermatologic, renal, hematologic, pulmonary, immune, cardiovascular,&#xD;
             gastrointestinal, genitourinary, neurologic, or psychiatric disorder, as determined by&#xD;
             the Investigator and/or Sponsor's medical monitor (MM) to be clinically significant&#xD;
             (CS.)&#xD;
&#xD;
          -  Any evidence of progressive liver disease (within the last 4 weeks prior to dosing)&#xD;
&#xD;
          -  Severe or uncontrolled medical conditions within 4 weeks prior to AG-120 dosing, with&#xD;
             the exception of illness related to HI.&#xD;
&#xD;
        Healthy Matched Subjects&#xD;
&#xD;
          -  Clinical evidence of liver disease or liver injury&#xD;
&#xD;
          -  History or presence of impaired renal function&#xD;
&#xD;
          -  QTCF &gt;450 (males) or &gt;460 (females) or ECG findings deemed abnormal by the&#xD;
             Investigator&#xD;
&#xD;
          -  Use of any prescription medications within 30 days prior to dosing&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>DaVita Clinical Research- Colorado</name>
      <address>
        <city>Lakewood</city>
        <state>Colorado</state>
        <zip>80228</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>DaVita Clinical Research- Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2018</verification_date>
  <study_first_submitted>September 8, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 14, 2017</study_first_posted>
  <last_update_submitted>April 26, 2018</last_update_submitted>
  <last_update_submitted_qc>April 26, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">April 27, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>AG-120</keyword>
  <keyword>Healthy Volunteer</keyword>
  <keyword>Clinical Pharmacology</keyword>
  <keyword>Hepatic Impairment</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ivosidenib</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03282513
org study id: AG120-C-012
nct id: NCT03282513
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Study AG120-C-012 is a Phase 1, open-label, single-dose study designed to evaluate the PK,
      safety, and tolerability of a single 500 mg AG-120 (Ivosidenib) dose in subjects with mild or
      moderate hepatic impairment (HI) compared to subjects with normal hepatic function. The study
      will be conducted at 2 US centers.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum observed plasma concentration (Cmax)
time frame: Predose; 0.5hr, 1hr, 2hr, 3hr, 4hr, 6hr, 9hr, 12hr, 24hr, 48hr, 72hr, 120hr, 168hr, 240hr, 336hr, and 504hr post dose
description: AG-120 Cmax, derived from plasma concentration-time curves
measure: Area under plasma concentration-time curve (AUC)
time frame: Predose; 0.5hr, 1hr, 2hr, 3hr, 4hr, 6hr, 9hr, 12hr, 24hr, 48hr, 72hr, 120hr, 168hr, 240hr, 336hr, and 504hr post dose
description: AG-120 AUC, derived from plasma concentration-time curves
measure: Adverse Events (AE) and treatment-related AE
time frame: From the time of study drug administration through the end of study (Day 29 or early termination)
measure: Plasma Protein Binding
time frame: Time Frame: Pre-dose, Day 1 and Day 2
description: Compare the plasma protein binding of AG-120 (Ivosidenib) in subjects with impaired HI with that in subjects with normal hepatic function.
arm group label: Cohort 1A: Mild Hepatic Impairment
arm group type: Experimental
description: Drug: AG-120 (Ivosidenib)
A single 500 mg oral dose of AG-120 (Ivosidenib) in subjects with mild hepatic impairment(Child-Pugh Score A.)
arm group label: Cohort 1B: Healthy Volunteers
arm group type: Active Comparator
description: Drug: AG-120 (Ivosidenib)
A single 500 mg oral dose of AG-120 (Ivosidenib) in subjects with normal hepatic function.
arm group label: Cohort 2A: Moderate Hepatic Impairment
arm group type: Experimental
description: Drug: AG-120 (Ivosidenib)
A single 500 mg oral dose of AG-120 (Ivosidenib) in subjects with moderate hepatic impairment (Child-Pugh Score B.)
arm group label: Cohort 2B: Healthy Volunteers
arm group type: Active Comparator
description: Drug: AG-120 (Ivosidenib)
A single 500 mg oral dose of AG-120 (Ivosidenib) in subjects with normal hepatic function.
intervention type: Drug
intervention name: AG-120 (Ivosidenib)
description: Single 500 mg dose of AG-120 (Ivosidenib).
arm group label: Cohort 1A: Mild Hepatic Impairment
arm group label: Cohort 1B: Healthy Volunteers
arm group label: Cohort 2A: Moderate Hepatic Impairment
arm group label: Cohort 2B: Healthy Volunteers
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Liver Diseases
mesh term: Ivosidenib