<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/NCT02989857</url>
  </required_header>
  <id_info>
    <org_study_id>AG120-C-005</org_study_id>
    <nct_id>NCT02989857</nct_id>
  </id_info>
  <brief_title>Study of AG-120 in Previously Treated Advanced Cholangiocarcinoma With IDH1 Mutations (ClarIDHy)</brief_title>
  <acronym>ClarIDHy</acronym>
  <official_title>A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-controlled Study of AG-120 in Previously-treated Subjects With Nonresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut de Recherches Internationales Servier</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Servier</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>
      Study AG120-C-005 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled&#xD;
      study of orally administered AG-120. Participants, all personnel involved in the evaluation&#xD;
      of participants' response to treatment (e.g., Investigators, study coordinators, study&#xD;
      pharmacists), and designated Sponsor team members will be blinded to study treatment.&#xD;
      Participants are required to have a histologically-confirmed diagnosis of isocitrate&#xD;
      dehydrogenase-1 (IDH1) gene-mutated cholangiocarcinoma that is not eligible for curative&#xD;
      resection, transplantation, or ablative therapies prior to enrollment. IDH1 mutation testing&#xD;
      will be performed at participating investigative sites. Participants must have progression of&#xD;
      disease and have received at least 1 but not more than 2 prior treatment regimens for&#xD;
      advanced disease (nonresectable or metastatic). All participants must have received either a&#xD;
      gemcitabine or a 5 fluorouracil (5-FU) based chemotherapy regimen.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 20, 2017</start_date>
  <completion_date type="Actual">May 17, 2021</completion_date>
  <primary_completion_date type="Actual">January 31, 2019</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Patients randomized in a 2:1 allocation (AG-120 vs Placebo)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression Free Survival (PFS) as Determined by the Independent Radiology Committee (IRC)</measure>
    <time_frame>From the date of randomization to the date of first documentation of disease progression or death due to any cause (Up to approximately 2 years)</time_frame>
    <description>PFS is defined as the time from date of randomization to the date of first documented disease progression as assessed by the IRC using Response Evaluation Criteria in Solid Tumors [RECIST] v1.1, or date of death due to any cause, whichever occurred first. Disease progression was defined as greater than or equal to (≥)20 percent (%) increase in sum of the diameter of target lesions, taking as reference the smallest sum diameter recorded since the treatment started. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm) or the appearance of 1 or more new lesions.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)</measure>
    <time_frame>From first dose of study drug up to 28 days after last dose for each intervention (Up to approximately 4 Years)</time_frame>
    <description>An AE is any untoward medical occurrence associated with the use of a drug in participants, whether or not considered drug related. An AE or suspected adverse reaction is considered serious (an SAE) if it is fatal, life-threatening, causes in-patient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect in a neonate/infant born to a mother or father exposed to study treatment or is an important medical event. Treatment-emergent adverse events are reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Experienced Laboratory Abnormalities Reported as Grade 3 or Higher Adverse Events</measure>
    <time_frame>From first dose of the study drug up to end of treatment visit for each intervention (Up to approximately 4 Years)</time_frame>
    <description>The laboratory parameters evaluated by the investigator included hematology and chemistry. Laboratory abnormalities reported in this endpoint are Grade 3 or higher adverse events. Grading categories were determined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Clinically Significant Grade 3 or Higher Vital Signs AEs</measure>
    <time_frame>From first dose of the study drug up to end of treatment visit for each intervention (Up to approximately 4 Years)</time_frame>
    <description>Clinically significant vital signs were recorded as adverse events; there were some vital signs reported as Grade 3 or higher adverse events. Grading categories were determined by NCI CTCAE, version 4.03.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status</measure>
    <time_frame>Baseline</time_frame>
    <description>The Eastern Cooperative Oncology Group Performance Status (ECOG PS) score classified participants according to their functional impairment, with scores ranging from 0 to 4. ECOG PS: 0 = fully active, able to carry on all pre-disease performance without restriction; 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work; 2 = ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3 = capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = completely disabled, cannot carry on any self-care, totally confined to bed or chair. A higher score means a worse functional status.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Required At Least One Concomitant Medications During the Treatment</measure>
    <time_frame>From first dose of study drug up to 28 days after last dose (Up to approximately 4 Years)</time_frame>
    <description>Concomitant medications were medications that were ongoing or initiated after the first dose of the study drug but before the last dose plus 28 days. Percentage of participants who required at least one concomitant medications during the study along with their prescribed study drug (AG-120 or placebo) were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Abnormal Electrocardiogram (ECG) Changes Reported as Adverse Events</measure>
    <time_frame>Pre-dose C1D1, C2D1; Post-dose C1D1, C1D15, C2D1 and Day 1 of C3D1 and all cycles thereafter up to last dose plus 28 days (Up to approximately 4 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>From date of randomization until the date of death due to any cause (Up to approximately 2 years)</time_frame>
    <description>Overall survival was defined as the time in months from date of randomization to the date of death due to any cause. Participants without documentation of death at the time of the final collection were censored at the date the participant was last known to be alive, or the final collection date, whichever is earlier.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) as Assessed by the Investigator RECIST Version 1.1</measure>
    <time_frame>From the date of randomization up to confirmed CR or PR (Up to approximately 2 years)</time_frame>
    <description>ORR as assessed by the investigator was defined as the percentage of participants with a best overall response (BOR) defined as complete response (CR) or partial response (PR) per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis &lt;10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR as Assessed by the IRC Per RECIST v1.1</measure>
    <time_frame>From the date of randomization up to confirmed CR or PR (Up to approximately 2 years)</time_frame>
    <description>ORR as assessed by the IRC was defined as the percentage of participants with a best overall response (BOR) defined as complete response (CR) or partial response (PR) per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis &lt;10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR) as Assessed by the Investigator</measure>
    <time_frame>From the date of first confirmed CR or PR to disease progression or death regardless of cause (Up to approximately 2 years)</time_frame>
    <description>DOR was defined as the time in months from date of first documented CR or PR to date of first documented disease progression or death due to any cause, whichever is earlier, as assessed by the Investigator per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis &lt;10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline. Participants with response and without progression were censored at the last observation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DOR as Assessed by the IRC Per RECIST v1.1</measure>
    <time_frame>From the date of first confirmed CR or PR to disease progression or death regardless of cause (Up to approximately 2 years)</time_frame>
    <description>DOR was defined as the time in months from date of first documented CR or PR to date of first documented disease progression or death due to any cause, whichever is earlier, as assessed by the IRC per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis &lt;10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline. Participants with response and without progression were censored at the last observation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Response (TTR) as Assessed by the Investigator</measure>
    <time_frame>From the date of randomization up to the date of first documented CR or PR (Up to approximately 2 years)</time_frame>
    <description>TTR was defined as the time from date of randomization to date of first documented CR or PR for responders, as assessed by the Investigator per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis &lt;10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline. Only responders were analyzed for this outcome measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TTR as Assessed by the IRC Per RECIST v1.1</measure>
    <time_frame>From the date of randomization up to the date of first documented CR or PR (Up to approximately 2 years)</time_frame>
    <description>TTR was defined as the time from date of randomization to date of first documented CR or PR for responders, as assessed by the IRC per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis &lt;10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline. Only responders were analyzed for this outcome measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS as Determined by Investigator</measure>
    <time_frame>From the date of randomization to the date of first documentation of disease progression or death due to any cause (Up to approximately 2 years)</time_frame>
    <description>PFS was defined as the time from date of randomization to the date of first documented disease progression as assessed by the investigator using RECIST v1.1, or date of death due to any cause, whichever occurred first. Disease progression was defined as ≥20% increase in sum of the diameter of target lesions, taking as reference the smallest sum diameter recorded since the treatment started. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm or the appearance of 1 or more new lesions. No progression or death by data cutoff date was censored at the last adequate assessment date.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Health-Related Quality of Life (HRQOL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30 Subscales Scores</measure>
    <time_frame>Cycle 2 Day 1 and Cycle 3 Day 1</time_frame>
    <description>EORTC-QLQ-C30 is the European Organization for Research and Treatment of Cancer - Quality of Life Questionnaire - Core Questionnaire. For EORTC QLQ-C30, subscales of physical functioning, pain, and appetite loss were assessed. These had 4 response levels (not at all, a little, quite a bit, and very much). For functional scales, higher scores=better QOL (positive change from Baseline=improvement). For symptom scales, lower scores=better QOL (negative change from Baseline=improvement). Using linear transformation, raw scores were standardized, so that scores ranged from 0 to 100.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in HRQOL Based on: Quality of Life Questionnaire - Cholangiocarcinoma and Gallbladder Cancer Module (QLQ-BIL21)</measure>
    <time_frame>Cycle 2 Day 1 and Cycle 3 Day 1</time_frame>
    <description>For HRQOL based on QLQ-BIL21, subscales of eating symptoms and pain symptoms were assessed. Each item is a 4-point Likert scale. There are 4 response levels (not at all, a little, quite a bit, and very much). Raw scores are converted into scale scores ranging from 0 to 100. For symptom scales, lower scores=better QOL (negative change from Baseline=improvement).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Change Based on HRQOL: Patient Global Impression of Change (PGI-C)</measure>
    <time_frame>Cycle 2 Day 1 and Cycle 3 Day 1</time_frame>
    <description>The PGI-C is a self-rated evaluative instrument for assessment across 3 domains (physical function, appetite loss, and pain). The PGI-C is measured using a 7-point Likert scale, with 6= very much better, 5= moderately better, 4= a little better, 3= no change, 2= a little worse, 1= moderately worse, and 0= very much worse. A lower score indicates a worse outcome. Percentages are rounded off to whole number at the nearest decimal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Severity Based on HRQOL: Patient Global Impression of Severity (PGI-S)</measure>
    <time_frame>Cycle 2 Day 1 and Cycle 3 Day 1</time_frame>
    <description>The anchor-based questionnaire PGI-S contains the following 3 items (the severity of the physical functioning decline over the past week, the severity of the appetite decrease over the past week, and the severity of the pain over the past week). The PGI-S was measured using the possible outcomes none, mild, moderate, severe, and very severe. Percentages are rounded off to whole number at the nearest decimal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Each EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) Dimension Response</measure>
    <time_frame>Cycle 3 Day 1</time_frame>
    <description>The EQ-5D-5L assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Percentages are rounded off to whole number at the nearest decimal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in EQ-5D-5L Visual Analogue Scale (EQ-5D-5L VAS) Score</measure>
    <time_frame>Cycle 3 Day 1</time_frame>
    <description>The EQ visual analogue scale records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled &quot;The best health you can imagine&quot; and &quot;The worst health you can imagine.&quot; Responses are marked on a 0-100 scale with higher scores indicating higher health-related quality of life (i.e., better outcome).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax) of AG-120</measure>
    <time_frame>Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)</time_frame>
    <description>Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Maximal Plasma Concentration (Tmax) of AG-120</measure>
    <time_frame>Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)</time_frame>
    <description>Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24)</measure>
    <time_frame>Post-dose of Cycle 2 Day 1 (each cycle = 28 days)</time_frame>
    <description>Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve From Time Zero to 4 Hours (AUC0-4)</measure>
    <time_frame>Post-dose of Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)</time_frame>
    <description>Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation Ratio Based on AUC0-4 (Racc AUC0-4)</measure>
    <time_frame>Post-dose Cycle 2 Day 1 (each cycle = 28 days)</time_frame>
    <description>Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation Ratio Based on Cmax (Racc Cmax)</measure>
    <time_frame>Post-dose Cycle 2 Day 1 (each cycle = 28 days)</time_frame>
    <description>Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: B (Baseline Effect Value)</measure>
    <time_frame>Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)</time_frame>
    <description>B is the Baseline Effect Value. Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: AUEC0-4</measure>
    <time_frame>Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)</time_frame>
    <description>AUEC0-4 is the area of the response curve from time point zero (predose) up to 4 hr postdose. Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: %BAUEC0-4</measure>
    <time_frame>Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)</time_frame>
    <description>%BAUEC0-4 is the percent inhibition for AUEC0-4. Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: Rtrough</measure>
    <time_frame>Post-dose Cycle 2 Day 1 (each cycle = 28 days)</time_frame>
    <description>Rtrough is the observed response value at the end of a dosing interval. Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: %BRtrough</measure>
    <time_frame>Post-dose Cycle 2 Day 1 (each cycle = 28 days)</time_frame>
    <description>%BRtrough is the percent inhibition for Rtrough. Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">187</enrollment>
  <condition>Advanced Cholangiocarcinoma</condition>
  <condition>Metastatic Cholangiocarcinoma</condition>
  <arm_group>
    <arm_group_label>AG-120</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants received AG-120 500 mg, tablet, orally, once a day (QD) in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 45 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 7 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>After Cross over to AG-120</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants who experienced disease progression and received placebo were allowed to cross over to receive AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle for up to approximately 32 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AG-120</intervention_name>
    <description>Tablet administered orally</description>
    <arm_group_label>AG-120</arm_group_label>
    <arm_group_label>After Cross over to AG-120</arm_group_label>
    <other_name>Ivosidenib</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Tablet administered orally</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Be ≥18 years of age.&#xD;
&#xD;
          2. Have a histopathological diagnosis (fresh or banked tumor biopsy sample, preferably&#xD;
             collected within the last 3 years) of nonresectable or metastatic cholangiocarcinoma&#xD;
             and are not eligible for curative resection, transplantation, or ablative therapies.&#xD;
&#xD;
          3. Have documented IDH1 gene-mutated disease (from a fresh tumor biopsy or the most&#xD;
             recent banked tumor tissue available) based on central laboratory testing&#xD;
             (R132C/L/G/H/S mutation variants tested).&#xD;
&#xD;
          4. Have an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or&#xD;
             1&#xD;
&#xD;
          5. Have an expected survival of ≥3 months.&#xD;
&#xD;
          6. Have at least one evaluable and measurable lesion as defined by Response Evaluation&#xD;
             Criteria in Solid Tumors (RECIST) v1.1. Participants who have received prior local&#xD;
             therapy (including but not limited to embolization, chemoembolization, radiofrequency&#xD;
             ablation, or radiation therapy) are eligible provided measurable disease falls outside&#xD;
             of the treatment field or within the field and has shown ≥20% growth in size since&#xD;
             post-treatment assessment.&#xD;
&#xD;
          7. Have documented disease progression following at least 1 and no more than 2 prior&#xD;
             systemic regimens for advanced disease (nonresectable or metastatic). Participants&#xD;
             must have received at least 1 gemcitabine- or 5-FU-containing regimen for advanced&#xD;
             cholangiocarcinoma. Participants who have received systemic adjuvant chemotherapy will&#xD;
             be permitted provided there is documented disease progression during or within 6&#xD;
             months of completing the therapy.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Received a prior IDH inhibitor.&#xD;
&#xD;
          2. Received systemic anticancer therapy or an investigational agent &lt;2 weeks prior to Day&#xD;
             1 (washout from prior immune based anticancer therapy is 4 weeks). In addition, the&#xD;
             first dose of study treatment should not occur before a period ≥5 half-lives of the&#xD;
             investigational agent has elapsed.&#xD;
&#xD;
          3. Received radiotherapy to metastatic sites of disease &lt;2 weeks prior to Day 1.&#xD;
&#xD;
          4. Underwent hepatic radiation, chemoembolization, and radiofrequency ablation &lt;4 weeks&#xD;
             prior to Day 1.&#xD;
&#xD;
          5. Have known symptomatic brain metastases requiring steroids. Participants with&#xD;
             previously diagnosed brain metastases are eligible if they have completed their&#xD;
             treatment and have recovered from the acute effects of radiation therapy or surgery&#xD;
             prior to study entry, have discontinued corticosteroid treatment for these metastases&#xD;
             for at least 4 weeks and have radiographically stable disease for at least 3 months&#xD;
             prior to study entry. Note: up to 10 mg per day of prednisone equivalent will be&#xD;
             allowed.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Affairs Servier Pharmaceuticals LLC</last_name>
    <role>Study Chair</role>
    <affiliation>Servier Pharmaceuticals, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Cancer Center</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City of Hope Cancer Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, Irvine</name>
      <address>
        <city>Irvine</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Southern California</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94158</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Cancer Center</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Cancer Center</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan-Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Taussig Cancer Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fox Chase Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gibbs Cancer Center</name>
      <address>
        <city>Spartanburg</city>
        <state>South Carolina</state>
        <zip>29303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas, SouthWestern</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah, Huntsman Cancer Institute</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seattle Cancer Care Alliance</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin, Carbone Cancer Center</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universite de Franche-Comte</name>
      <address>
        <city>Besançon</city>
        <zip>25000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre de Lutte Contre le Cancer (CLCC) - Institut Bergonie</name>
      <address>
        <city>Bordeaux</city>
        <zip>33076</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Eugene Marquis Centre Regional de Lutte Contre Le Cancer</name>
      <address>
        <city>Rennes</city>
        <zip>35042</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <zip>94805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione del Piemonte per l'Oncologia - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS Candiolo)</name>
      <address>
        <city>Candiolo</city>
        <zip>10060</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Scientifico Universitario San Raffaele</name>
      <address>
        <city>Milano</city>
        <zip>20127</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Clinico Humanitas</name>
      <address>
        <city>Rozzano</city>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yonsei University Severance Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul, St. Mary's Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>06591</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Center</name>
      <address>
        <city>Seoul</city>
        <zip>10408</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Vall d'Hebrón</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario Gregorio Marañón</name>
      <address>
        <city>Madrid</city>
        <zip>28007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario 12 de Octubre</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Integral Oncologico Clara Campal</name>
      <address>
        <city>Madrid</city>
        <zip>28050</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Marques de Valdecilla</name>
      <address>
        <city>Santander</city>
        <zip>39008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. James University Hospital</name>
      <address>
        <city>Leeds</city>
        <zip>LS16 6QB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Liverpool Cancer Center</name>
      <address>
        <city>Liverpool</city>
        <zip>CH63 4JY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University College London Hospitals</name>
      <address>
        <city>London</city>
        <zip>NW1 2PG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Royal Free Hospital</name>
      <address>
        <city>London</city>
        <zip>NW3 2QG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Christie NHS Foundation Trust, the Christie Hospital</name>
      <address>
        <city>Manchester</city>
        <zip>M20 4QL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
    <country>Italy</country>
    <country>Korea, Republic of</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>December 5, 2016</study_first_submitted>
  <study_first_submitted_qc>December 8, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 12, 2016</study_first_posted>
  <results_first_submitted>January 28, 2022</results_first_submitted>
  <results_first_submitted_qc>March 18, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">April 13, 2022</results_first_posted>
  <disposition_first_submitted>January 30, 2020</disposition_first_submitted>
  <disposition_first_submitted_qc>March 18, 2022</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">April 13, 2022</disposition_first_posted>
  <last_update_submitted>December 20, 2022</last_update_submitted>
  <last_update_submitted_qc>December 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>IDH1</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cholangiocarcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ivosidenib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.&#xD;
Access can be requested for all interventional clinical studies:&#xD;
used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).&#xD;
where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.&#xD;
In addition, access can be requested for all interventional clinical studies in patients:&#xD;
sponsored by Servier&#xD;
with a first patient enrolled as of 1 January 2004 onwards&#xD;
for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>After Marketing Authorisation in EEA or US if the study is used for the approval.</ipd_time_frame>
    <ipd_access_criteria>Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.</ipd_access_criteria>
    <ipd_url>https://clinicaltrials.servier.com/</ipd_url>
  </patient_data>
  <study_docs>
    <study_doc>
      <doc_type>Individual Participant Data Set</doc_type>
      <doc_url>https://clinicaltrials.servier.com/</doc_url>
    </study_doc>
    <study_doc>
      <doc_type>Study Protocol</doc_type>
      <doc_url>https://clinicaltrials.servier.com/</doc_url>
    </study_doc>
    <study_doc>
      <doc_type>Statistical Analysis Plan</doc_type>
      <doc_url>https://clinicaltrials.servier.com/</doc_url>
    </study_doc>
    <study_doc>
      <doc_type>Informed Consent Form</doc_type>
      <doc_url>https://clinicaltrials.servier.com/</doc_url>
    </study_doc>
    <study_doc>
      <doc_type>Clinical Study Report</doc_type>
      <doc_url>https://clinicaltrials.servier.com/</doc_url>
    </study_doc>
    <study_doc>
      <doc_type>Study-level clinical trial data</doc_type>
      <doc_url>https://clinicaltrials.servier.com/</doc_url>
    </study_doc>
  </study_docs>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol: Protocol v6</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>March 5, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/57/NCT02989857/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol: Protocol v7</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 23, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/57/NCT02989857/Prot_002.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>April 1, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/57/NCT02989857/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants took part in the study at 49 study sites in France, Italy, Spain, South Korea, the United States, and the United Kingdom from 20 February 2017 to 17 May 2021.</recruitment_details>
      <pre_assignment_details>The final analysis of progression-free survival (PFS) occurred once 131 PFS events had been determined by Investigator assessment. Two participants were randomized in the study after the data cutoff date (31 January 2019) for the final analysis of PFS.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>AG-120</title>
          <description>Participants received AG-120 500 mg, tablet, orally, once daily (QD) in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 45 months.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 7 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.</description>
        </group>
        <group group_id="P3">
          <title>After Crossover to AG-120</title>
          <description>Participants who experienced disease progression and received placebo were allowed to cross over to receive AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle for up to approximately 32 months.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Randomization Phase</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="126"/>
                <participants group_id="P2" count="61"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="123">Completed = Participants who completed the protocol defined treatment.</participants>
                <participants group_id="P2" count="59">Completed = Participants who completed the protocol defined treatment.</participants>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Not Treated</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Cross Over Phase</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="43">Participants who had experienced disease progression and received placebo were allowed to cross over to receive AG-120.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="43">Completed = Participants who completed the protocol defined treatment.</participants>
              </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_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Intent-To-Treat (ITT) Set included all participants who were randomized, with the treatment group designated according to the randomization.</population>
      <group_list>
        <group group_id="B1">
          <title>AG-120</title>
          <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 45 months.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 7 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="126"/>
            <count group_id="B2" value="61"/>
            <count group_id="B3" value="187"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="60.3" spread="10.97"/>
                    <measurement group_id="B2" value="62.9" spread="10.38"/>
                    <measurement group_id="B3" value="61.1" spread="10.82"/>
                  </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="82"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="119"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="44"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Ethnicity</title>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="84"/>
                    <measurement group_id="B2" value="40"/>
                    <measurement group_id="B3" value="124"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Race</title>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="71"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="106"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Progression Free Survival (PFS) as Determined by the Independent Radiology Committee (IRC)</title>
        <description>PFS is defined as the time from date of randomization to the date of first documented disease progression as assessed by the IRC using Response Evaluation Criteria in Solid Tumors [RECIST] v1.1, or date of death due to any cause, whichever occurred first. Disease progression was defined as greater than or equal to (≥)20 percent (%) increase in sum of the diameter of target lesions, taking as reference the smallest sum diameter recorded since the treatment started. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm) or the appearance of 1 or more new lesions.</description>
        <time_frame>From the date of randomization to the date of first documentation of disease progression or death due to any cause (Up to approximately 2 years)</time_frame>
        <population>ITT set included all participants who were randomized, with the treatment group designated according to the randomization. Number analyzed is the number of participants with data available for analyses at the specified time point. Two participants were excluded from the analysis as they were randomized in the study after the data cutoff date (31 January 2019) for the analysis of PFS.</population>
        <group_list>
          <group group_id="O1">
            <title>AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 45 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 7 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS) as Determined by the Independent Radiology Committee (IRC)</title>
          <description>PFS is defined as the time from date of randomization to the date of first documented disease progression as assessed by the IRC using Response Evaluation Criteria in Solid Tumors [RECIST] v1.1, or date of death due to any cause, whichever occurred first. Disease progression was defined as greater than or equal to (≥)20 percent (%) increase in sum of the diameter of target lesions, taking as reference the smallest sum diameter recorded since the treatment started. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm) or the appearance of 1 or more new lesions.</description>
          <population>ITT set included all participants who were randomized, with the treatment group designated according to the randomization. Number analyzed is the number of participants with data available for analyses at the specified time point. Two participants were excluded from the analysis as they were randomized in the study after the data cutoff date (31 January 2019) for the analysis of PFS.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="124"/>
                <count group_id="O2" value="61"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.7" lower_limit="1.6" upper_limit="4.2"/>
                    <measurement group_id="O2" value="1.4" lower_limit="1.4" upper_limit="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>P-value was calculated from the one-sided stratified log-rank test.</p_value_desc>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.37</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.25</ci_lower_limit>
            <ci_upper_limit>0.54</ci_upper_limit>
            <estimate_desc>Hazard ratio was calculated from stratified Cox regression model with placebo as the denominator, with two-sided 95% confidence interval.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)</title>
        <description>An AE is any untoward medical occurrence associated with the use of a drug in participants, whether or not considered drug related. An AE or suspected adverse reaction is considered serious (an SAE) if it is fatal, life-threatening, causes in-patient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect in a neonate/infant born to a mother or father exposed to study treatment or is an important medical event. Treatment-emergent adverse events are reported.</description>
        <time_frame>From first dose of study drug up to 28 days after last dose for each intervention (Up to approximately 4 Years)</time_frame>
        <population>Safety Analysis Set (SAS) included all participants who received at least one dose of study drug (AG-120 or Placebo).</population>
        <group_list>
          <group group_id="O1">
            <title>AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 45 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 7 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.</description>
          </group>
          <group group_id="O3">
            <title>After Crossover to AG-120</title>
            <description>Participants who experienced disease progression and received placebo were allowed to cross over to receive AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle for up to approximately 32 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)</title>
          <description>An AE is any untoward medical occurrence associated with the use of a drug in participants, whether or not considered drug related. An AE or suspected adverse reaction is considered serious (an SAE) if it is fatal, life-threatening, causes in-patient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect in a neonate/infant born to a mother or father exposed to study treatment or is an important medical event. Treatment-emergent adverse events are reported.</description>
          <population>Safety Analysis Set (SAS) included all participants who received at least one dose of study drug (AG-120 or Placebo).</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="123"/>
                <count group_id="O2" value="59"/>
                <count group_id="O3" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="97.6"/>
                    <measurement group_id="O2" value="96.6"/>
                    <measurement group_id="O3" value="95.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.0"/>
                    <measurement group_id="O2" value="23.7"/>
                    <measurement group_id="O3" value="27.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Experienced Laboratory Abnormalities Reported as Grade 3 or Higher Adverse Events</title>
        <description>The laboratory parameters evaluated by the investigator included hematology and chemistry. Laboratory abnormalities reported in this endpoint are Grade 3 or higher adverse events. Grading categories were determined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.</description>
        <time_frame>From first dose of the study drug up to end of treatment visit for each intervention (Up to approximately 4 Years)</time_frame>
        <population>SAS included all participants who received at least one dose of study drug (AG-120 or Placebo).</population>
        <group_list>
          <group group_id="O1">
            <title>AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 45 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 7 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.</description>
          </group>
          <group group_id="O3">
            <title>After Crossover to AG-120</title>
            <description>Participants who experienced disease progression and received placebo were allowed to cross over to receive AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle for up to approximately 32 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Experienced Laboratory Abnormalities Reported as Grade 3 or Higher Adverse Events</title>
          <description>The laboratory parameters evaluated by the investigator included hematology and chemistry. Laboratory abnormalities reported in this endpoint are Grade 3 or higher adverse events. Grading categories were determined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.</description>
          <population>SAS included all participants who received at least one dose of study drug (AG-120 or Placebo).</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="123"/>
                <count group_id="O2" value="59"/>
                <count group_id="O3" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Anaemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.3"/>
                    <measurement group_id="O2" value="0.0"/>
                    <measurement group_id="O3" value="9.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelet Count Decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4"/>
                    <measurement group_id="O2" value="0.0"/>
                    <measurement group_id="O3" value="2.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophil Count Decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6"/>
                    <measurement group_id="O2" value="0.0"/>
                    <measurement group_id="O3" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White Blood Cell Count Decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6"/>
                    <measurement group_id="O2" value="0.0"/>
                    <measurement group_id="O3" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocyte Count Decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8"/>
                    <measurement group_id="O2" value="3.4"/>
                    <measurement group_id="O3" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Thrombocytopenia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8"/>
                    <measurement group_id="O2" value="0.0"/>
                    <measurement group_id="O3" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood Loss Anaemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8"/>
                    <measurement group_id="O2" value="0.0"/>
                    <measurement group_id="O3" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood Bilirubin Increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.7"/>
                    <measurement group_id="O2" value="1.7"/>
                    <measurement group_id="O3" value="7.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyponatraemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.7"/>
                    <measurement group_id="O2" value="10.2"/>
                    <measurement group_id="O3" value="2.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Aspartate Aminotransferase Increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.9"/>
                    <measurement group_id="O2" value="1.7"/>
                    <measurement group_id="O3" value="4.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypophosphataemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.3"/>
                    <measurement group_id="O2" value="5.1"/>
                    <measurement group_id="O3" value="4.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyperbilirubinaemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.3"/>
                    <measurement group_id="O2" value="0.0"/>
                    <measurement group_id="O3" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyperkalaemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4"/>
                    <measurement group_id="O2" value="3.4"/>
                    <measurement group_id="O3" value="2.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood Alkaline Phosphatase Increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4"/>
                    <measurement group_id="O2" value="5.1"/>
                    <measurement group_id="O3" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alanine Aminotransferase Increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6"/>
                    <measurement group_id="O2" value="0.0"/>
                    <measurement group_id="O3" value="2.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypoalbuminaemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6"/>
                    <measurement group_id="O2" value="1.7"/>
                    <measurement group_id="O3" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gamma-glutamyltransferase Increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8"/>
                    <measurement group_id="O2" value="1.7"/>
                    <measurement group_id="O3" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypercalcaemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8"/>
                    <measurement group_id="O2" value="1.7"/>
                    <measurement group_id="O3" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyperuricaemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8"/>
                    <measurement group_id="O2" value="0.0"/>
                    <measurement group_id="O3" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypokalaemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8"/>
                    <measurement group_id="O2" value="1.7"/>
                    <measurement group_id="O3" value="2.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Transaminases Increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8"/>
                    <measurement group_id="O2" value="0.0"/>
                    <measurement group_id="O3" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood Uric Acid Increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0"/>
                    <measurement group_id="O2" value="1.7"/>
                    <measurement group_id="O3" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Clinically Significant Grade 3 or Higher Vital Signs AEs</title>
        <description>Clinically significant vital signs were recorded as adverse events; there were some vital signs reported as Grade 3 or higher adverse events. Grading categories were determined by NCI CTCAE, version 4.03.</description>
        <time_frame>From first dose of the study drug up to end of treatment visit for each intervention (Up to approximately 4 Years)</time_frame>
        <population>SAS included all participants who received at least one dose of study drug (AG-120 or Placebo).</population>
        <group_list>
          <group group_id="O1">
            <title>AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 45 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 7 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.</description>
          </group>
          <group group_id="O3">
            <title>After Crossover to AG-120</title>
            <description>Participants who experienced disease progression and received placebo were allowed to cross over to receive AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle for up to approximately 32 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Clinically Significant Grade 3 or Higher Vital Signs AEs</title>
          <description>Clinically significant vital signs were recorded as adverse events; there were some vital signs reported as Grade 3 or higher adverse events. Grading categories were determined by NCI CTCAE, version 4.03.</description>
          <population>SAS included all participants who received at least one dose of study drug (AG-120 or Placebo).</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="123"/>
                <count group_id="O2" value="59"/>
                <count group_id="O3" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pyrexia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8"/>
                    <measurement group_id="O2" value="0.0"/>
                    <measurement group_id="O3" value="2.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Weight Decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8"/>
                    <measurement group_id="O2" value="1.7"/>
                    <measurement group_id="O3" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypertension</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6"/>
                    <measurement group_id="O2" value="1.7"/>
                    <measurement group_id="O3" value="7.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypotension</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6"/>
                    <measurement group_id="O2" value="1.7"/>
                    <measurement group_id="O3" value="2.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status</title>
        <description>The Eastern Cooperative Oncology Group Performance Status (ECOG PS) score classified participants according to their functional impairment, with scores ranging from 0 to 4. ECOG PS: 0 = fully active, able to carry on all pre-disease performance without restriction; 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work; 2 = ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3 = capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = completely disabled, cannot carry on any self-care, totally confined to bed or chair. A higher score means a worse functional status.</description>
        <time_frame>Baseline</time_frame>
        <population>ITT population included all participants who were randomized, with the treatment group designated according to the randomization.</population>
        <group_list>
          <group group_id="O1">
            <title>AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 45 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 7 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status</title>
          <description>The Eastern Cooperative Oncology Group Performance Status (ECOG PS) score classified participants according to their functional impairment, with scores ranging from 0 to 4. ECOG PS: 0 = fully active, able to carry on all pre-disease performance without restriction; 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work; 2 = ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3 = capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = completely disabled, cannot carry on any self-care, totally confined to bed or chair. A higher score means a worse functional status.</description>
          <population>ITT population included all participants who were randomized, with the treatment group designated according to the randomization.</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="126"/>
                <count group_id="O2" value="61"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.7"/>
                    <measurement group_id="O2" value="31.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59.5"/>
                    <measurement group_id="O2" value="67.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0"/>
                    <measurement group_id="O2" value="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Required At Least One Concomitant Medications During the Treatment</title>
        <description>Concomitant medications were medications that were ongoing or initiated after the first dose of the study drug but before the last dose plus 28 days. Percentage of participants who required at least one concomitant medications during the study along with their prescribed study drug (AG-120 or placebo) were reported.</description>
        <time_frame>From first dose of study drug up to 28 days after last dose (Up to approximately 4 Years)</time_frame>
        <population>SAS included all participants who received at least one dose of study drug (AG-120 or Placebo).</population>
        <group_list>
          <group group_id="O1">
            <title>AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 45 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 7 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.</description>
          </group>
          <group group_id="O3">
            <title>After Crossover to AG-120</title>
            <description>Participants who experienced disease progression and received placebo were allowed to cross over to receive AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle for up to approximately 32 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Required At Least One Concomitant Medications During the Treatment</title>
          <description>Concomitant medications were medications that were ongoing or initiated after the first dose of the study drug but before the last dose plus 28 days. Percentage of participants who required at least one concomitant medications during the study along with their prescribed study drug (AG-120 or placebo) were reported.</description>
          <population>SAS included all participants who received at least one dose of study drug (AG-120 or Placebo).</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="123"/>
                <count group_id="O2" value="59"/>
                <count group_id="O3" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="99.2"/>
                    <measurement group_id="O2" value="98.3"/>
                    <measurement group_id="O3" value="95.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Abnormal Electrocardiogram (ECG) Changes Reported as Adverse Events</title>
        <time_frame>Pre-dose C1D1, C2D1; Post-dose C1D1, C1D15, C2D1 and Day 1 of C3D1 and all cycles thereafter up to last dose plus 28 days (Up to approximately 4 years)</time_frame>
        <population>SAS included all participants who received at least one dose of study drug (AG-120 or Placebo).</population>
        <group_list>
          <group group_id="O1">
            <title>AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 45 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 7 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.</description>
          </group>
          <group group_id="O3">
            <title>After Crossover to AG-120</title>
            <description>Participants who experienced disease progression and received placebo were allowed to cross over to receive AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle for up to approximately 32 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Abnormal Electrocardiogram (ECG) Changes Reported as Adverse Events</title>
          <population>SAS included all participants who received at least one dose of study drug (AG-120 or Placebo).</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="123"/>
                <count group_id="O2" value="59"/>
                <count group_id="O3" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Electrocardiogram QT Prolonged</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.8"/>
                    <measurement group_id="O2" value="3.4"/>
                    <measurement group_id="O3" value="2.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Electrocardiogram Abnormal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8"/>
                    <measurement group_id="O2" value="0.0"/>
                    <measurement group_id="O3" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>Overall survival was defined as the time in months from date of randomization to the date of death due to any cause. Participants without documentation of death at the time of the final collection were censored at the date the participant was last known to be alive, or the final collection date, whichever is earlier.</description>
        <time_frame>From date of randomization until the date of death due to any cause (Up to approximately 2 years)</time_frame>
        <population>ITT population included all participants who were randomized, with the treatment group designated according to the randomization.</population>
        <group_list>
          <group group_id="O1">
            <title>AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 45 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 7 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>Overall survival was defined as the time in months from date of randomization to the date of death due to any cause. Participants without documentation of death at the time of the final collection were censored at the date the participant was last known to be alive, or the final collection date, whichever is earlier.</description>
          <population>ITT population included all participants who were randomized, with the treatment group designated according to the randomization.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="126"/>
                <count group_id="O2" value="61"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.3" lower_limit="7.8" upper_limit="12.4"/>
                    <measurement group_id="O2" value="7.5" lower_limit="4.8" upper_limit="11.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.093</p_value>
            <p_value_desc>P-value was calculated from the one-sided stratified log-rank test. Stratification factor was the number of prior line of therapies at randomization.</p_value_desc>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.79</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.56</ci_lower_limit>
            <ci_upper_limit>1.12</ci_upper_limit>
            <estimate_desc>Hazard ratio was calculated from the stratified Cox regression model with placebo as the comparator, with two-sided 95% CI. Stratification factor was the number of prior line of therapies at randomization.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Objective Response Rate (ORR) as Assessed by the Investigator RECIST Version 1.1</title>
        <description>ORR as assessed by the investigator was defined as the percentage of participants with a best overall response (BOR) defined as complete response (CR) or partial response (PR) per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis &lt;10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline.</description>
        <time_frame>From the date of randomization up to confirmed CR or PR (Up to approximately 2 years)</time_frame>
        <population>ITT population included all participants who were randomized, with the treatment group designated according to the randomization. Number analyzed is the number of participants with data available for analyses at the specified time point. Two participants were excluded from the analysis as they were randomized in the study after the data cutoff date (31 January 2019) for the analysis of tumor response.</population>
        <group_list>
          <group group_id="O1">
            <title>AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 45 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 7 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR) as Assessed by the Investigator RECIST Version 1.1</title>
          <description>ORR as assessed by the investigator was defined as the percentage of participants with a best overall response (BOR) defined as complete response (CR) or partial response (PR) per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis &lt;10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline.</description>
          <population>ITT population included all participants who were randomized, with the treatment group designated according to the randomization. Number analyzed is the number of participants with data available for analyses at the specified time point. Two participants were excluded from the analysis as they were randomized in the study after the data cutoff date (31 January 2019) for the analysis of tumor response.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="124"/>
                <count group_id="O2" value="61"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.2" lower_limit="0.9" upper_limit="8.1"/>
                    <measurement group_id="O2" value="1.6" lower_limit="0.0" upper_limit="8.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.466</p_value>
            <p_value_desc>P-value was calculated from 1-sided Fisher exact test.</p_value_desc>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>ORR as Assessed by the IRC Per RECIST v1.1</title>
        <description>ORR as assessed by the IRC was defined as the percentage of participants with a best overall response (BOR) defined as complete response (CR) or partial response (PR) per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis &lt;10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline.</description>
        <time_frame>From the date of randomization up to confirmed CR or PR (Up to approximately 2 years)</time_frame>
        <population>ITT population included all participants who were randomized, with the treatment group designated according to the randomization. Number analyzed is the number of participants with data available for analyses at the specified time point. Two participants were excluded from the analysis as they were randomized in the study after the data cutoff date (31 January 2019) for the analysis of tumor response.</population>
        <group_list>
          <group group_id="O1">
            <title>AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 45 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 7 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.</description>
          </group>
        </group_list>
        <measure>
          <title>ORR as Assessed by the IRC Per RECIST v1.1</title>
          <description>ORR as assessed by the IRC was defined as the percentage of participants with a best overall response (BOR) defined as complete response (CR) or partial response (PR) per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis &lt;10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline.</description>
          <population>ITT population included all participants who were randomized, with the treatment group designated according to the randomization. Number analyzed is the number of participants with data available for analyses at the specified time point. Two participants were excluded from the analysis as they were randomized in the study after the data cutoff date (31 January 2019) for the analysis of tumor response.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="124"/>
                <count group_id="O2" value="61"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4" lower_limit="0.5" upper_limit="6.9"/>
                    <measurement group_id="O2" value="0" lower_limit="0.0" upper_limit="5.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.299</p_value>
            <p_value_desc>P-value was calculated from 1-sided Fisher exact test.</p_value_desc>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response (DOR) as Assessed by the Investigator</title>
        <description>DOR was defined as the time in months from date of first documented CR or PR to date of first documented disease progression or death due to any cause, whichever is earlier, as assessed by the Investigator per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis &lt;10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline. Participants with response and without progression were censored at the last observation.</description>
        <time_frame>From the date of first confirmed CR or PR to disease progression or death regardless of cause (Up to approximately 2 years)</time_frame>
        <population>Participants with CR or PR per investigator assessment by the data cutoff date (31 January 2019) for the analysis of tumor response.</population>
        <group_list>
          <group group_id="O1">
            <title>AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 45 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 7 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response (DOR) as Assessed by the Investigator</title>
          <description>DOR was defined as the time in months from date of first documented CR or PR to date of first documented disease progression or death due to any cause, whichever is earlier, as assessed by the Investigator per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis &lt;10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline. Participants with response and without progression were censored at the last observation.</description>
          <population>Participants with CR or PR per investigator assessment by the data cutoff date (31 January 2019) for the analysis of tumor response.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">Median, lower limit and upper limit were not available due to the insufficient number of participants with events.</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="NA" upper_limit="NA">Median, lower limit and upper limit were not available due to the insufficient number of participants with events.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>DOR as Assessed by the IRC Per RECIST v1.1</title>
        <description>DOR was defined as the time in months from date of first documented CR or PR to date of first documented disease progression or death due to any cause, whichever is earlier, as assessed by the IRC per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis &lt;10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline. Participants with response and without progression were censored at the last observation.</description>
        <time_frame>From the date of first confirmed CR or PR to disease progression or death regardless of cause (Up to approximately 2 years)</time_frame>
        <population>Participants with CR or PR per investigator assessment by the data cutoff date (31 January 2019) for the analysis of tumor response.</population>
        <group_list>
          <group group_id="O1">
            <title>AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 45 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 7 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.</description>
          </group>
        </group_list>
        <measure>
          <title>DOR as Assessed by the IRC Per RECIST v1.1</title>
          <description>DOR was defined as the time in months from date of first documented CR or PR to date of first documented disease progression or death due to any cause, whichever is earlier, as assessed by the IRC per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis &lt;10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline. Participants with response and without progression were censored at the last observation.</description>
          <population>Participants with CR or PR per investigator assessment by the data cutoff date (31 January 2019) for the analysis of tumor response.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">Median, lower limit and upper limit were not available due to the insufficient number of participants with events.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Response (TTR) as Assessed by the Investigator</title>
        <description>TTR was defined as the time from date of randomization to date of first documented CR or PR for responders, as assessed by the Investigator per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis &lt;10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline. Only responders were analyzed for this outcome measure.</description>
        <time_frame>From the date of randomization up to the date of first documented CR or PR (Up to approximately 2 years)</time_frame>
        <population>Participants with CR or PR per investigator assessment by the data cutoff date (31 January 2019) were analyzed for tumor response.</population>
        <group_list>
          <group group_id="O1">
            <title>AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 45 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 7 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Response (TTR) as Assessed by the Investigator</title>
          <description>TTR was defined as the time from date of randomization to date of first documented CR or PR for responders, as assessed by the Investigator per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis &lt;10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline. Only responders were analyzed for this outcome measure.</description>
          <population>Participants with CR or PR per investigator assessment by the data cutoff date (31 January 2019) were analyzed for tumor response.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">Median, upper and lower limit were not available due to the insufficient number of participants with events.</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="NA" upper_limit="NA">Median, upper and lower limit were not available due to the insufficient number of participants with events.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>TTR as Assessed by the IRC Per RECIST v1.1</title>
        <description>TTR was defined as the time from date of randomization to date of first documented CR or PR for responders, as assessed by the IRC per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis &lt;10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline. Only responders were analyzed for this outcome measure.</description>
        <time_frame>From the date of randomization up to the date of first documented CR or PR (Up to approximately 2 years)</time_frame>
        <population>Participants with CR or PR per investigator assessment by the data cutoff date (31 January 2019) were analyzed for tumor response.</population>
        <group_list>
          <group group_id="O1">
            <title>AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 45 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 7 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.</description>
          </group>
        </group_list>
        <measure>
          <title>TTR as Assessed by the IRC Per RECIST v1.1</title>
          <description>TTR was defined as the time from date of randomization to date of first documented CR or PR for responders, as assessed by the IRC per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis &lt;10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline. Only responders were analyzed for this outcome measure.</description>
          <population>Participants with CR or PR per investigator assessment by the data cutoff date (31 January 2019) were analyzed for tumor response.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">Median, upper and lower limit were not available due to the insufficient number of participants with events.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PFS as Determined by Investigator</title>
        <description>PFS was defined as the time from date of randomization to the date of first documented disease progression as assessed by the investigator using RECIST v1.1, or date of death due to any cause, whichever occurred first. Disease progression was defined as ≥20% increase in sum of the diameter of target lesions, taking as reference the smallest sum diameter recorded since the treatment started. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm or the appearance of 1 or more new lesions. No progression or death by data cutoff date was censored at the last adequate assessment date.</description>
        <time_frame>From the date of randomization to the date of first documentation of disease progression or death due to any cause (Up to approximately 2 years)</time_frame>
        <population>ITT set included all participants who were randomized, with the treatment group designated according to the randomization. Number analyzed is the number of participants with data available for analyses at the specified time point. Two participants were excluded from the analysis as they were randomized in the study after the data cutoff date (31 January 2019) for the analysis of PFS.</population>
        <group_list>
          <group group_id="O1">
            <title>AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 45 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 7 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.</description>
          </group>
        </group_list>
        <measure>
          <title>PFS as Determined by Investigator</title>
          <description>PFS was defined as the time from date of randomization to the date of first documented disease progression as assessed by the investigator using RECIST v1.1, or date of death due to any cause, whichever occurred first. Disease progression was defined as ≥20% increase in sum of the diameter of target lesions, taking as reference the smallest sum diameter recorded since the treatment started. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm or the appearance of 1 or more new lesions. No progression or death by data cutoff date was censored at the last adequate assessment date.</description>
          <population>ITT set included all participants who were randomized, with the treatment group designated according to the randomization. Number analyzed is the number of participants with data available for analyses at the specified time point. Two participants were excluded from the analysis as they were randomized in the study after the data cutoff date (31 January 2019) for the analysis of PFS.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="124"/>
                <count group_id="O2" value="61"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.7" lower_limit="1.6" upper_limit="3.6"/>
                    <measurement group_id="O2" value="1.4" lower_limit="1.4" upper_limit="2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>P-value was calculated from one-sided stratified log-rank test. Stratification factor was the number of prior line of therapies at randomization.</p_value_desc>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.47</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.33</ci_lower_limit>
            <ci_upper_limit>0.68</ci_upper_limit>
            <estimate_desc>Hazard ratio was calculated from the stratified Cox regression model with placebo as the denominator, with two-sided 95% CI. Stratification factor was the number of prior line of therapies at randomization.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Health-Related Quality of Life (HRQOL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30 Subscales Scores</title>
        <description>EORTC-QLQ-C30 is the European Organization for Research and Treatment of Cancer - Quality of Life Questionnaire - Core Questionnaire. For EORTC QLQ-C30, subscales of physical functioning, pain, and appetite loss were assessed. These had 4 response levels (not at all, a little, quite a bit, and very much). For functional scales, higher scores=better QOL (positive change from Baseline=improvement). For symptom scales, lower scores=better QOL (negative change from Baseline=improvement). Using linear transformation, raw scores were standardized, so that scores ranged from 0 to 100.</description>
        <time_frame>Cycle 2 Day 1 and Cycle 3 Day 1</time_frame>
        <population>ITT population included all randomized participants, with treatment group designated according to the randomization. Overall Number of Participants Analyzed is the number of participants with data available for analyses at baseline and the given post-baseline timepoints. Number Analyzed at a particular timepoint is the number of participants with data available for analyses at baseline and given timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 45 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 7 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Health-Related Quality of Life (HRQOL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30 Subscales Scores</title>
          <description>EORTC-QLQ-C30 is the European Organization for Research and Treatment of Cancer - Quality of Life Questionnaire - Core Questionnaire. For EORTC QLQ-C30, subscales of physical functioning, pain, and appetite loss were assessed. These had 4 response levels (not at all, a little, quite a bit, and very much). For functional scales, higher scores=better QOL (positive change from Baseline=improvement). For symptom scales, lower scores=better QOL (negative change from Baseline=improvement). Using linear transformation, raw scores were standardized, so that scores ranged from 0 to 100.</description>
          <population>ITT population included all randomized participants, with treatment group designated according to the randomization. Overall Number of Participants Analyzed is the number of participants with data available for analyses at baseline and the given post-baseline timepoints. Number Analyzed at a particular timepoint is the number of participants with data available for analyses at baseline and given timepoint.</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="73"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 2 Day 1: Physical Functioning</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.4" spread="1.75"/>
                    <measurement group_id="O2" value="-13.3" spread="2.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 1: Pain</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.2" spread="2.48"/>
                    <measurement group_id="O2" value="12.5" spread="4.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 1: Appetite Loss</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.9" spread="2.60"/>
                    <measurement group_id="O2" value="4.3" spread="4.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 3 Day 1: Physical Functioning</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.2" spread="1.89"/>
                    <measurement group_id="O2" value="-12.6" spread="3.88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 3 Day 1: Pain</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.2" spread="2.73"/>
                    <measurement group_id="O2" value="-5.3" spread="5.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 3 Day 1: Appetite Loss</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5" spread="2.89"/>
                    <measurement group_id="O2" value="3.2" spread="6.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Cycle 2 Day 1: Physical Functioning</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Least-squares mean difference</param_type>
            <param_value>11.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>4.23</ci_lower_limit>
            <ci_upper_limit>17.73</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Cycle 2 Day 1: Pain</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Least-squares mean difference</param_type>
            <param_value>-10.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-20.18</ci_lower_limit>
            <ci_upper_limit>-0.52</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Cycle 2 Day 1: Appetite Loss</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Least-squares mean difference</param_type>
            <param_value>3.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-6.65</ci_lower_limit>
            <ci_upper_limit>13.91</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Cycle 3 Day 1: Physical Functioning</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Least-squares mean difference</param_type>
            <param_value>12.3</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>3.85</ci_lower_limit>
            <ci_upper_limit>20.78</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Cycle 3 Day 1: Pain</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Least-squares mean difference</param_type>
            <param_value>4.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-8.74</ci_lower_limit>
            <ci_upper_limit>17.04</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Cycle 3 Day 1: Appetite Loss</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Least-squares mean difference</param_type>
            <param_value>-3.7</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-17.46</ci_lower_limit>
            <ci_upper_limit>10.11</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in HRQOL Based on: Quality of Life Questionnaire - Cholangiocarcinoma and Gallbladder Cancer Module (QLQ-BIL21)</title>
        <description>For HRQOL based on QLQ-BIL21, subscales of eating symptoms and pain symptoms were assessed. Each item is a 4-point Likert scale. There are 4 response levels (not at all, a little, quite a bit, and very much). Raw scores are converted into scale scores ranging from 0 to 100. For symptom scales, lower scores=better QOL (negative change from Baseline=improvement).</description>
        <time_frame>Cycle 2 Day 1 and Cycle 3 Day 1</time_frame>
        <population>ITT population included all randomized participants, with treatment group designated according to the randomization. Overall Number of Participants Analyzed is the number of participants with data available for analyses at baseline and the given post-baseline timepoints. Number Analyzed at a particular timepoint is the number of participants with data available for analyses at baseline and given timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 45 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 7 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in HRQOL Based on: Quality of Life Questionnaire - Cholangiocarcinoma and Gallbladder Cancer Module (QLQ-BIL21)</title>
          <description>For HRQOL based on QLQ-BIL21, subscales of eating symptoms and pain symptoms were assessed. Each item is a 4-point Likert scale. There are 4 response levels (not at all, a little, quite a bit, and very much). Raw scores are converted into scale scores ranging from 0 to 100. For symptom scales, lower scores=better QOL (negative change from Baseline=improvement).</description>
          <population>ITT population included all randomized participants, with treatment group designated according to the randomization. Overall Number of Participants Analyzed is the number of participants with data available for analyses at baseline and the given post-baseline timepoints. Number Analyzed at a particular timepoint is the number of participants with data available for analyses at baseline and given timepoint.</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="70"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 2 Day 1: Pain</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="65"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.1" spread="1.94"/>
                    <measurement group_id="O2" value="10.1" spread="3.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 1: Appetite Loss</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="65"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.3" spread="1.84"/>
                    <measurement group_id="O2" value="3.6" spread="3.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 3 Day 1: Pain</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="48"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.3" spread="2.16"/>
                    <measurement group_id="O2" value="-2.1" spread="4.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 3 Day 1: Appetite Loss</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="48"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0" spread="2.02"/>
                    <measurement group_id="O2" value="4.1" spread="4.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Cycle 2 Day 1: Pain</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Least-squares mean difference</param_type>
            <param_value>-5.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-12.93</ci_lower_limit>
            <ci_upper_limit>2.80</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Cycle 2 Day 1: Appetite Loss</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Least-squares mean difference</param_type>
            <param_value>0.7</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-6.56</ci_lower_limit>
            <ci_upper_limit>7.88</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Cycle 3 Day 1: Pain</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Least-squares mean difference</param_type>
            <param_value>4.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-5.82</ci_lower_limit>
            <ci_upper_limit>14.55</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Cycle 3 Day 1: Appetite Loss</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Least-squares mean difference</param_type>
            <param_value>-6.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-15.34</ci_lower_limit>
            <ci_upper_limit>3.12</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Change Based on HRQOL: Patient Global Impression of Change (PGI-C)</title>
        <description>The PGI-C is a self-rated evaluative instrument for assessment across 3 domains (physical function, appetite loss, and pain). The PGI-C is measured using a 7-point Likert scale, with 6= very much better, 5= moderately better, 4= a little better, 3= no change, 2= a little worse, 1= moderately worse, and 0= very much worse. A lower score indicates a worse outcome. Percentages are rounded off to whole number at the nearest decimal.</description>
        <time_frame>Cycle 2 Day 1 and Cycle 3 Day 1</time_frame>
        <population>ITT population included all participants who were randomized, with the treatment group designated according to the randomization. Overall number analyzed is the number of participants available for analysis. Number analyzed is the number of participants available for analysis at the given timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 45 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 7 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Change Based on HRQOL: Patient Global Impression of Change (PGI-C)</title>
          <description>The PGI-C is a self-rated evaluative instrument for assessment across 3 domains (physical function, appetite loss, and pain). The PGI-C is measured using a 7-point Likert scale, with 6= very much better, 5= moderately better, 4= a little better, 3= no change, 2= a little worse, 1= moderately worse, and 0= very much worse. A lower score indicates a worse outcome. Percentages are rounded off to whole number at the nearest decimal.</description>
          <population>ITT population included all participants who were randomized, with the treatment group designated according to the randomization. Overall number analyzed is the number of participants available for analysis. Number analyzed is the number of participants available for analysis at the given timepoint.</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="67"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Physical Change: Cycle 2 Day 1: Very Much Worse</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Change: Cycle 2 Day 1: Moderately Worse</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.5"/>
                    <measurement group_id="O2" value="13.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Change: Cycle 2 Day 1: A Little Worse</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.4"/>
                    <measurement group_id="O2" value="9.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Change: Cycle 2 Day 1: No Change</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38.8"/>
                    <measurement group_id="O2" value="27.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Change: Cycle 2 Day 1: A Little Better</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.4"/>
                    <measurement group_id="O2" value="36.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Change: Cycle 2 Day 1: Moderately Better</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.0"/>
                    <measurement group_id="O2" value="9.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Change: Cycle 2 Day 1: Very Much Better</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5"/>
                    <measurement group_id="O2" value="4.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Change: Cycle 3 Day 1: Very Much Worse</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Change: Cycle 3 Day 1: Moderately Worse</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.9"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Change: Cycle 3 Day 1: A Little Worse</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.9"/>
                    <measurement group_id="O2" value="8.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Change: Cycle 3 Day 1: No Change</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.2"/>
                    <measurement group_id="O2" value="58.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Change: Cycle 3 Day 1: A Little Better</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.4"/>
                    <measurement group_id="O2" value="16.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Change: Cycle 3 Day 1: Moderately Better</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.7"/>
                    <measurement group_id="O2" value="16.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Change: Cycle 3 Day 1: Very Much Better</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite Change: Cycle 2 Day 1: Very Much Worse</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite Change: Cycle 2 Day 1: Moderately Worse</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.5"/>
                    <measurement group_id="O2" value="4.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite Change: Cycle 2 Day 1: A Little Worse</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.9"/>
                    <measurement group_id="O2" value="18.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite Change: Cycle 2 Day 1: No Change</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50.7"/>
                    <measurement group_id="O2" value="45.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite Change: Cycle 2 Day 1: A Little Better</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.4"/>
                    <measurement group_id="O2" value="13.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite Change: Cycle 2 Day 1: Moderately Better</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.5"/>
                    <measurement group_id="O2" value="9.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite Change: Cycle 2 Day 1: Very Much Better</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5"/>
                    <measurement group_id="O2" value="9.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite Change: Cycle 3 Day 1: Very Much Worse</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite Change: Cycle 3 Day 1: Moderately Worse</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.9"/>
                    <measurement group_id="O2" value="8.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite Change: Cycle 3 Day 1: A Little Worse</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.9"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite Change: Cycle 3 Day 1: No Change</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="64.7"/>
                    <measurement group_id="O2" value="50.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite Change: Cycle 3 Day 1: A Little Better</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.8"/>
                    <measurement group_id="O2" value="25.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite Change: Cycle 3 Day 1: Moderately Better</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.8"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite Change: Cycle 3 Day 1: Very Much Better</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.9"/>
                    <measurement group_id="O2" value="16.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Change: Cycle 2 Day 1: Very Much Worse</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Change: Cycle 2 Day 1: Moderately Worse</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.0"/>
                    <measurement group_id="O2" value="13.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Change: Cycle 2 Day 1: A Little Worse</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.0"/>
                    <measurement group_id="O2" value="9.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Change: Cycle 2 Day 1: No Change</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="64.2"/>
                    <measurement group_id="O2" value="54.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Change: Cycle 2 Day 1: A Little Better</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.5"/>
                    <measurement group_id="O2" value="18.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Change: Cycle 2 Day 1: Moderately Better</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.4"/>
                    <measurement group_id="O2" value="4.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Change: Cycle 2 Day 1: Very Much Better</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Change: Cycle 3 Day 1: Very Much Worse</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Change: Cycle 3 Day 1: Moderately Worse</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.9"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Change: Cycle 3 Day 1: A Little Worse</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.8"/>
                    <measurement group_id="O2" value="8.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Change: Cycle 3 Day 1: No Change</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60.8"/>
                    <measurement group_id="O2" value="66.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Change: Cycle 3 Day 1: A Little Better</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.8"/>
                    <measurement group_id="O2" value="8.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Change: Cycle 3 Day 1: Moderately Better</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.8"/>
                    <measurement group_id="O2" value="8.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Change: Cycle 3 Day 1: Very Much Better</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.9"/>
                    <measurement group_id="O2" value="8.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Severity Based on HRQOL: Patient Global Impression of Severity (PGI-S)</title>
        <description>The anchor-based questionnaire PGI-S contains the following 3 items (the severity of the physical functioning decline over the past week, the severity of the appetite decrease over the past week, and the severity of the pain over the past week). The PGI-S was measured using the possible outcomes none, mild, moderate, severe, and very severe. Percentages are rounded off to whole number at the nearest decimal.</description>
        <time_frame>Cycle 2 Day 1 and Cycle 3 Day 1</time_frame>
        <population>ITT population included all participants who were randomized, with the treatment group designated according to the randomization. Overall number analyzed is the number of participants available for analysis. Number analyzed is the number of participants available for analysis at the given timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 45 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 7 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Severity Based on HRQOL: Patient Global Impression of Severity (PGI-S)</title>
          <description>The anchor-based questionnaire PGI-S contains the following 3 items (the severity of the physical functioning decline over the past week, the severity of the appetite decrease over the past week, and the severity of the pain over the past week). The PGI-S was measured using the possible outcomes none, mild, moderate, severe, and very severe. Percentages are rounded off to whole number at the nearest decimal.</description>
          <population>ITT population included all participants who were randomized, with the treatment group designated according to the randomization. Overall number analyzed is the number of participants available for analysis. Number analyzed is the number of participants available for analysis at the given timepoint.</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="67"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Physical Decline: Cycle 2 Day 1: None</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="55.2"/>
                    <measurement group_id="O2" value="31.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Decline: Cycle 2 Day 1: Mild</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.9"/>
                    <measurement group_id="O2" value="27.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Decline: Cycle 2 Day 1: Moderate</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.4"/>
                    <measurement group_id="O2" value="31.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Decline: Cycle 2 Day 1: Severe</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.0"/>
                    <measurement group_id="O2" value="9.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Decline: Cycle 2 Day 1: Very Severe</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Decline: Cycle 3 Day 1: None</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70.6"/>
                    <measurement group_id="O2" value="75.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Decline: Cycle 3 Day 1: Mild</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.8"/>
                    <measurement group_id="O2" value="16.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Decline: Cycle 3 Day 1: Moderate</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.7"/>
                    <measurement group_id="O2" value="8.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Decline: Cycle 3 Day 1: Severe</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Decline: Cycle 3 Day 1: very Severe</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite Decrease: Cycle 2 Day 1: None</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53.7"/>
                    <measurement group_id="O2" value="45.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite Decrease: Cycle 2 Day 1: Mild</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.8"/>
                    <measurement group_id="O2" value="13.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite Decrease: Cycle 2 Day 1: Moderate</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.4"/>
                    <measurement group_id="O2" value="36.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite Decrease: Cycle 2 Day 1: Severe</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5"/>
                    <measurement group_id="O2" value="4.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite Decrease: Cycle 2 Day 1: Very Severe</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite Decrease: Cycle 3 Day 1: None</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70.6"/>
                    <measurement group_id="O2" value="58.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite Decrease: Cycle 3 Day 1: Mild</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.7"/>
                    <measurement group_id="O2" value="25.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite Decrease: Cycle 3 Day 1: Moderate</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.8"/>
                    <measurement group_id="O2" value="16.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite Decrease: Cycle 3 Day 1: Severe</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.9"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite Decrease: Cycle 3 Day 1: Very Severe</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Severity: Cycle 2 Day 1: None</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.8"/>
                    <measurement group_id="O2" value="31.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Severity: Cycle 2 Day 1: Mild</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38.8"/>
                    <measurement group_id="O2" value="13.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Severity: Cycle 2 Day 1: Moderate</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.9"/>
                    <measurement group_id="O2" value="40.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Severity: Cycle 2 Day 1: Severe</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.5"/>
                    <measurement group_id="O2" value="9.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Severity: Cycle 2 Day 1: Very Severe</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="67"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0"/>
                    <measurement group_id="O2" value="4.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Severity: Cycle 3 Day 1: None</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.2"/>
                    <measurement group_id="O2" value="33.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Severity: Cycle 3 Day 1: Mild</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.3"/>
                    <measurement group_id="O2" value="25.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Severity: Cycle 3 Day 1: Moderate</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.6"/>
                    <measurement group_id="O2" value="41.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Severity: Cycle 3 Day 1: Severe</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.8"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain Severity: Cycle 3 Day 1: Very Severe</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Each EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) Dimension Response</title>
        <description>The EQ-5D-5L assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Percentages are rounded off to whole number at the nearest decimal.</description>
        <time_frame>Cycle 3 Day 1</time_frame>
        <population>ITT population included all participants who were randomized, with the treatment group designated according to the randomization. Overall number analyzed is the number of participants available for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 45 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 7 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Each EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) Dimension Response</title>
          <description>The EQ-5D-5L assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Percentages are rounded off to whole number at the nearest decimal.</description>
          <population>ITT population included all participants who were randomized, with the treatment group designated according to the randomization. Overall number analyzed is the number of participants available for 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="50"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Mobility: No Problems Walking</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52.0"/>
                    <measurement group_id="O2" value="41.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mobility: Slight Problems Walking</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.0"/>
                    <measurement group_id="O2" value="25.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mobility: Moderate Problems Walking</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.0"/>
                    <measurement group_id="O2" value="33.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mobility: Severe Problems Walking</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.0"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mobility: Unable to Walk</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Self-Care: No Problems Washing or Dressing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="88.0"/>
                    <measurement group_id="O2" value="83.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Self-Care: Slight Problems Washing or Dressing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.0"/>
                    <measurement group_id="O2" value="16.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Self-Care: Moderate Problems Washing or Dressing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Self-Care: Severe Problems Washing or Dressing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Usual Activities: No Problems Doing Usual Activities</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.0"/>
                    <measurement group_id="O2" value="33.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Usual Activities: Slight Problems Doing Usual Activities</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34.0"/>
                    <measurement group_id="O2" value="41.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Usual Activities: Moderate Problems Doing Usual Activities</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.0"/>
                    <measurement group_id="O2" value="25.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Usual Activities: Severe Problems Doing Usual Activities</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.0"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Usual Activities: Unable to do Usual Activities</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain/Discomfort: No Pain or Discomfort</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.0"/>
                    <measurement group_id="O2" value="41.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain/Discomfort: Slight Pain or Discomfort</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.0"/>
                    <measurement group_id="O2" value="33.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain/Discomfort: Moderate Pain or Discomfort</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.0"/>
                    <measurement group_id="O2" value="25.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain/Discomfort: Severe Pain or Discomfort</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.0"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain/Discomfort: Extreme Pain or Discomfort</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0"/>
                    <measurement group_id="O2" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anxiety/Depression: Not Anxious or Depressed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50.0"/>
                    <measurement group_id="O2" value="33.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anxiety/Depression: Slightly Anxious or Depressed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.0"/>
                    <measurement group_id="O2" value="33.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anxiety/Depression: Moderately Anxious or Depressed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.0"/>
                    <measurement group_id="O2" value="25.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anxiety/Depression: Severely Anxious or Depressed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0"/>
                    <measurement group_id="O2" value="8.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in EQ-5D-5L Visual Analogue Scale (EQ-5D-5L VAS) Score</title>
        <description>The EQ visual analogue scale records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled &quot;The best health you can imagine&quot; and &quot;The worst health you can imagine.&quot; Responses are marked on a 0-100 scale with higher scores indicating higher health-related quality of life (i.e., better outcome).</description>
        <time_frame>Cycle 3 Day 1</time_frame>
        <population>ITT population included all participants who were randomized, with the treatment group designated according to the randomization. Overall number analyzed is the number of participants available for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 45 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 7 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in EQ-5D-5L Visual Analogue Scale (EQ-5D-5L VAS) Score</title>
          <description>The EQ visual analogue scale records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled &quot;The best health you can imagine&quot; and &quot;The worst health you can imagine.&quot; Responses are marked on a 0-100 scale with higher scores indicating higher health-related quality of life (i.e., better outcome).</description>
          <population>ITT population included all participants who were randomized, with the treatment group designated according to the randomization. Overall number analyzed is the number of participants available for analysis.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.6" spread="13.48"/>
                    <measurement group_id="O2" value="-2.8" spread="7.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Observed Plasma Concentration (Cmax) of AG-120</title>
        <description>Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.</description>
        <time_frame>Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)</time_frame>
        <population>Pharmacokinetic (PK) Analysis Population consisted of all participants who were enrolled and received at least one dose of study medication (AG-120) with sufficient plasma sample data to assess PK parameters. Number analyzed is the number of participants with data available for analyses at the specified time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Randomization Phase AG-120 Plus Cross Over Phase AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study. Participants who experienced disease progression and received placebo were allowed to cross over to receive AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Observed Plasma Concentration (Cmax) of AG-120</title>
          <description>Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.</description>
          <population>Pharmacokinetic (PK) Analysis Population consisted of all participants who were enrolled and received at least one dose of study medication (AG-120) with sufficient plasma sample data to assess PK parameters. Number analyzed is the number of participants with data available for analyses at the specified time point.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="142"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="142"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4424.0" spread="1808.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="107"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5050.5" spread="1666.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Reach Maximal Plasma Concentration (Tmax) of AG-120</title>
        <description>Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.</description>
        <time_frame>Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)</time_frame>
        <population>PK Analysis Population consisted of all participants who were enrolled and received at least one dose of study medication (AG-120) with sufficient plasma sample data to assess PK parameters. Number analyzed is the number of participants with data available for analyses at the specified time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Randomization Phase AG-120 Plus Cross Over Phase AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study. Participants who experienced disease progression and received placebo were allowed to cross over to receive AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Reach Maximal Plasma Concentration (Tmax) of AG-120</title>
          <description>Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.</description>
          <population>PK Analysis Population consisted of all participants who were enrolled and received at least one dose of study medication (AG-120) with sufficient plasma sample data to assess PK parameters. Number analyzed is the number of participants with data available for analyses at the specified time point.</population>
          <units>hours (h)</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="142"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="142"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.63" lower_limit="0.50" upper_limit="4.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="107"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.07" lower_limit="0.50" upper_limit="4.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24)</title>
        <description>Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.</description>
        <time_frame>Post-dose of Cycle 2 Day 1 (each cycle = 28 days)</time_frame>
        <population>PK Analysis Population consisted of all participants who were enrolled and received at least one dose of study medication (AG-120) with sufficient plasma sample data to assess PK parameters. Number analyzed is the number of participants with data available for analyses at the specified time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Randomization Phase AG-120 Plus Cross Over Phase AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study. Participants who experienced disease progression and received placebo were allowed to cross over to receive AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24)</title>
          <description>Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.</description>
          <population>PK Analysis Population consisted of all participants who were enrolled and received at least one dose of study medication (AG-120) with sufficient plasma sample data to assess PK parameters. Number analyzed is the number of participants with data available for analyses at the specified time point.</population>
          <units>h*ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="107"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="91219.4" spread="31574.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-time Curve From Time Zero to 4 Hours (AUC0-4)</title>
        <description>Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.</description>
        <time_frame>Post-dose of Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)</time_frame>
        <population>PK Analysis Population consisted of all participants who were enrolled and received at least one dose of study medication (AG-120) with sufficient plasma sample data to assess PK parameters. Number analyzed is the number of participants with data available for analyses at the specified time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Randomization Phase AG-120 Plus Cross Over Phase AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study. Participants who experienced disease progression and received placebo were allowed to cross over to receive AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Curve From Time Zero to 4 Hours (AUC0-4)</title>
          <description>Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.</description>
          <population>PK Analysis Population consisted of all participants who were enrolled and received at least one dose of study medication (AG-120) with sufficient plasma sample data to assess PK parameters. Number analyzed is the number of participants with data available for analyses at the specified time point.</population>
          <units>h*ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="141"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="141"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10972.2" spread="5044.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="106"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16651.7" spread="5269.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Accumulation Ratio Based on AUC0-4 (Racc AUC0-4)</title>
        <description>Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.</description>
        <time_frame>Post-dose Cycle 2 Day 1 (each cycle = 28 days)</time_frame>
        <population>PK Analysis Population consisted of all participants who were enrolled and received at least one dose of study medication (AG-120) with sufficient plasma sample data to assess PK parameters. Number analyzed is the number of participants with data available for analyses at the specified time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Randomization Phase AG-120 Plus Cross Over Phase AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study. Participants who experienced disease progression and received placebo were allowed to cross over to receive AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Accumulation Ratio Based on AUC0-4 (Racc AUC0-4)</title>
          <description>Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.</description>
          <population>PK Analysis Population consisted of all participants who were enrolled and received at least one dose of study medication (AG-120) with sufficient plasma sample data to assess PK parameters. Number analyzed is the number of participants with data available for analyses at the specified time point.</population>
          <units>ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6881" spread="0.83303"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Accumulation Ratio Based on Cmax (Racc Cmax)</title>
        <description>Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.</description>
        <time_frame>Post-dose Cycle 2 Day 1 (each cycle = 28 days)</time_frame>
        <population>PK Analysis Population consisted of all participants who were enrolled and received at least one dose of study medication (AG-120) with sufficient plasma sample data to assess PK parameters. Number analyzed is the number of participants with data available for analyses at the specified time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Randomization Phase AG-120 Plus Cross Over Phase AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study. Participants who experienced disease progression and received placebo were allowed to cross over to receive AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Accumulation Ratio Based on Cmax (Racc Cmax)</title>
          <description>Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.</description>
          <population>PK Analysis Population consisted of all participants who were enrolled and received at least one dose of study medication (AG-120) with sufficient plasma sample data to assess PK parameters. Number analyzed is the number of participants with data available for analyses at the specified time point.</population>
          <units>ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.2369" spread="0.50798"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: B (Baseline Effect Value)</title>
        <description>B is the Baseline Effect Value. Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.</description>
        <time_frame>Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)</time_frame>
        <population>Pharmacodynamic (PD) Analysis Population consisted of all participants who were enrolled and received any dose of study medication (AG-120) with sufficient plasma sample data to assess pharmacodynamic parameters. Number analyzed is the number of participants with data available for analyses at the specified time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Randomization Phase AG-120 Plus Cross Over Phase AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study. Participants who experienced disease progression and received placebo were allowed to cross over to receive AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: B (Baseline Effect Value)</title>
          <description>B is the Baseline Effect Value. Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.</description>
          <population>Pharmacodynamic (PD) Analysis Population consisted of all participants who were enrolled and received any dose of study medication (AG-120) with sufficient plasma sample data to assess pharmacodynamic parameters. Number analyzed is the number of participants with data available for analyses at the specified time point.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="142"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="142"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1107.70" spread="1709.919"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="108"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="795.09" spread="938.677"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: AUEC0-4</title>
        <description>AUEC0-4 is the area of the response curve from time point zero (predose) up to 4 hr postdose. Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.</description>
        <time_frame>Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)</time_frame>
        <population>PD Analysis Population consisted of all participants who were enrolled and received any dose of study medication (AG-120) with sufficient plasma sample data to assess pharmacodynamic parameters. Number analyzed is the number of participants with data available for analyses at the specified time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Randomization Phase AG-120 Plus Cross Over Phase AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study. Participants who experienced disease progression and received placebo were allowed to cross over to receive AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: AUEC0-4</title>
          <description>AUEC0-4 is the area of the response curve from time point zero (predose) up to 4 hr postdose. Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.</description>
          <population>PD Analysis Population consisted of all participants who were enrolled and received any dose of study medication (AG-120) with sufficient plasma sample data to assess pharmacodynamic parameters. Number analyzed is the number of participants with data available for analyses at the specified time point.</population>
          <units>h*ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="141"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="141"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3334.3" spread="4785.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="107"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="368.4" spread="278.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: %BAUEC0-4</title>
        <description>%BAUEC0-4 is the percent inhibition for AUEC0-4. Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.</description>
        <time_frame>Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)</time_frame>
        <population>PD Analysis Population consisted of all participants who were enrolled and received any dose of study medication (AG-120) with sufficient plasma sample data to assess pharmacodynamic parameters. Number analyzed is the number of participants with data available for analyses at the specified time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Randomization Phase AG-120 Plus Cross Over Phase AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study. Participants who experienced disease progression and received placebo were allowed to cross over to receive AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: %BAUEC0-4</title>
          <description>%BAUEC0-4 is the percent inhibition for AUEC0-4. Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.</description>
          <population>PD Analysis Population consisted of all participants who were enrolled and received any dose of study medication (AG-120) with sufficient plasma sample data to assess pharmacodynamic parameters. Number analyzed is the number of participants with data available for analyses at the specified time point.</population>
          <units>percent</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="141"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="141"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.22090" spread="10.13659"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="107"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="74.9750" spread="22.53852"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: Rtrough</title>
        <description>Rtrough is the observed response value at the end of a dosing interval. Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.</description>
        <time_frame>Post-dose Cycle 2 Day 1 (each cycle = 28 days)</time_frame>
        <population>PD Analysis Population consisted of all participants who were enrolled and received any dose of study medication (AG-120) with sufficient plasma sample data to assess pharmacodynamic parameters. Number analyzed is the number of participants with data available for analyses at the specified time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Randomization Phase AG-120 Plus Cross Over Phase AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study. Participants who experienced disease progression and received placebo were allowed to cross over to receive AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: Rtrough</title>
          <description>Rtrough is the observed response value at the end of a dosing interval. Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.</description>
          <population>PD Analysis Population consisted of all participants who were enrolled and received any dose of study medication (AG-120) with sufficient plasma sample data to assess pharmacodynamic parameters. Number analyzed is the number of participants with data available for analyses at the specified time point.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="108"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="97.66" spread="72.838"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: %BRtrough</title>
        <description>%BRtrough is the percent inhibition for Rtrough. Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.</description>
        <time_frame>Post-dose Cycle 2 Day 1 (each cycle = 28 days)</time_frame>
        <population>PD Analysis Population consisted of all participants who were enrolled and received any dose of study medication (AG-120) with sufficient plasma sample data to assess pharmacodynamic parameters. Number analyzed is the number of participants with data available for analyses at the specified time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Randomization Phase AG-120 Plus Cross Over Phase AG-120</title>
            <description>Participants received AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study. Participants who experienced disease progression and received placebo were allowed to cross over to receive AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: %BRtrough</title>
          <description>%BRtrough is the percent inhibition for Rtrough. Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.</description>
          <population>PD Analysis Population consisted of all participants who were enrolled and received any dose of study medication (AG-120) with sufficient plasma sample data to assess pharmacodynamic parameters. Number analyzed is the number of participants with data available for analyses at the specified time point.</population>
          <units>percent</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="108"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="73.726" spread="23.3113"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From first dose of study drug up to 28 days after last dose for each intervention (Up to approximately 4 years)</time_frame>
      <desc>All-Cause Mortality was assessed as per ITT population. Adverse Events: Safety Analysis Set included all participants who received at least one dose of study treatment.</desc>
      <group_list>
        <group group_id="E1">
          <title>AG-120</title>
          <description>Participants received AG-120 500 mg, tablet, orally, once daily (QD) in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 45 months.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 7 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.</description>
        </group>
        <group group_id="E3">
          <title>After Cross Over to AG-120</title>
          <description>Participants who experienced disease progression and received placebo were allowed to cross over to receive AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle for up to approximately 32 months.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 23.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="99" subjects_at_risk="126"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="61"/>
                <counts group_id="E3" subjects_affected="34" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="43" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="12" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Blood loss anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Tachyarrhythmia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Abdominal pain lower</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Intestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Intestinal pseudo-obstruction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Large intestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Oesophageal varices haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Upper gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Localised oedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Biliary obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Bile duct stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Cholangitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Cholangitis acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Hepatic cirrhosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Hepatic failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Hepatic haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Hyperbilirubinaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Jaundice</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Jaundice cholestatic</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Abdominal infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Bacteraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Bacterial infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Biliary sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Biliary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Clostridium difficile colitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Escherichia bacteraemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Parainfluenzae virus infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Staphylococcal infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Systemic candida</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Wound infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Arterial injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Hip fracture</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Failure to thrive</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cognitive disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Depressed level of consciousness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Hepatic encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Multiple sclerosis relapse</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Spinal cord compression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Thecal sac compression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Mental status changes</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Nephropathy toxic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 23.1</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="118" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="56" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="36" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="52" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="12" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="43" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="12" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="30" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="38" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="30" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Neuropathy peripheral</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="31" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="123"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="43"/>
              </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 information obtained from the clinical study will be used towards the development of ivosidenib and may be disclosed to regulatory authority(ies), other Investigators, corporate partners, or consultants as required.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Medical Affairs</name_or_title>
      <organization>Servier Pharmaceuticals LLC</organization>
      <phone>888-788-1735</phone>
      <email>clinical.trial.management@servier.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/NCT02989857
org study id: AG120-C-005
nct id: NCT02989857
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Study AG120-C-005 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled
      study of orally administered AG-120. Participants, all personnel involved in the evaluation
      of participants' response to treatment (e.g., Investigators, study coordinators, study
      pharmacists), and designated Sponsor team members will be blinded to study treatment.
      Participants are required to have a histologically-confirmed diagnosis of isocitrate
      dehydrogenase-1 (IDH1) gene-mutated cholangiocarcinoma that is not eligible for curative
      resection, transplantation, or ablative therapies prior to enrollment. IDH1 mutation testing
      will be performed at participating investigative sites. Participants must have progression of
      disease and have received at least 1 but not more than 2 prior treatment regimens for
      advanced disease (nonresectable or metastatic). All participants must have received either a
      gemcitabine or a 5 fluorouracil (5-FU) based chemotherapy regimen.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Patients randomized in a 2:1 allocation (AG-120 vs Placebo)
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Progression Free Survival (PFS) as Determined by the Independent Radiology Committee (IRC)
time frame: From the date of randomization to the date of first documentation of disease progression or death due to any cause (Up to approximately 2 years)
description: PFS is defined as the time from date of randomization to the date of first documented disease progression as assessed by the IRC using Response Evaluation Criteria in Solid Tumors [RECIST] v1.1, or date of death due to any cause, whichever occurred first. Disease progression was defined as greater than or equal to (≥)20 percent (%) increase in sum of the diameter of target lesions, taking as reference the smallest sum diameter recorded since the treatment started. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm) or the appearance of 1 or more new lesions.
measure: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
time frame: From first dose of study drug up to 28 days after last dose for each intervention (Up to approximately 4 Years)
description: An AE is any untoward medical occurrence associated with the use of a drug in participants, whether or not considered drug related. An AE or suspected adverse reaction is considered serious (an SAE) if it is fatal, life-threatening, causes in-patient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect in a neonate/infant born to a mother or father exposed to study treatment or is an important medical event. Treatment-emergent adverse events are reported.
measure: Percentage of Participants Who Experienced Laboratory Abnormalities Reported as Grade 3 or Higher Adverse Events
time frame: From first dose of the study drug up to end of treatment visit for each intervention (Up to approximately 4 Years)
description: The laboratory parameters evaluated by the investigator included hematology and chemistry. Laboratory abnormalities reported in this endpoint are Grade 3 or higher adverse events. Grading categories were determined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.
measure: Percentage of Participants With Clinically Significant Grade 3 or Higher Vital Signs AEs
time frame: From first dose of the study drug up to end of treatment visit for each intervention (Up to approximately 4 Years)
description: Clinically significant vital signs were recorded as adverse events; there were some vital signs reported as Grade 3 or higher adverse events. Grading categories were determined by NCI CTCAE, version 4.03.
measure: Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status
time frame: Baseline
description: The Eastern Cooperative Oncology Group Performance Status (ECOG PS) score classified participants according to their functional impairment, with scores ranging from 0 to 4. ECOG PS: 0 = fully active, able to carry on all pre-disease performance without restriction; 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work; 2 = ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3 = capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = completely disabled, cannot carry on any self-care, totally confined to bed or chair. A higher score means a worse functional status.
measure: Percentage of Participants Who Required At Least One Concomitant Medications During the Treatment
time frame: From first dose of study drug up to 28 days after last dose (Up to approximately 4 Years)
description: Concomitant medications were medications that were ongoing or initiated after the first dose of the study drug but before the last dose plus 28 days. Percentage of participants who required at least one concomitant medications during the study along with their prescribed study drug (AG-120 or placebo) were reported.
measure: Percentage of Participants With Abnormal Electrocardiogram (ECG) Changes Reported as Adverse Events
time frame: Pre-dose C1D1, C2D1; Post-dose C1D1, C1D15, C2D1 and Day 1 of C3D1 and all cycles thereafter up to last dose plus 28 days (Up to approximately 4 years)
measure: Overall Survival (OS)
time frame: From date of randomization until the date of death due to any cause (Up to approximately 2 years)
description: Overall survival was defined as the time in months from date of randomization to the date of death due to any cause. Participants without documentation of death at the time of the final collection were censored at the date the participant was last known to be alive, or the final collection date, whichever is earlier.
measure: Objective Response Rate (ORR) as Assessed by the Investigator RECIST Version 1.1
time frame: From the date of randomization up to confirmed CR or PR (Up to approximately 2 years)
description: ORR as assessed by the investigator was defined as the percentage of participants with a best overall response (BOR) defined as complete response (CR) or partial response (PR) per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis <10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline.
measure: ORR as Assessed by the IRC Per RECIST v1.1
time frame: From the date of randomization up to confirmed CR or PR (Up to approximately 2 years)
description: ORR as assessed by the IRC was defined as the percentage of participants with a best overall response (BOR) defined as complete response (CR) or partial response (PR) per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis <10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline.
measure: Duration of Response (DOR) as Assessed by the Investigator
time frame: From the date of first confirmed CR or PR to disease progression or death regardless of cause (Up to approximately 2 years)
description: DOR was defined as the time in months from date of first documented CR or PR to date of first documented disease progression or death due to any cause, whichever is earlier, as assessed by the Investigator per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis <10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline. Participants with response and without progression were censored at the last observation.
measure: DOR as Assessed by the IRC Per RECIST v1.1
time frame: From the date of first confirmed CR or PR to disease progression or death regardless of cause (Up to approximately 2 years)
description: DOR was defined as the time in months from date of first documented CR or PR to date of first documented disease progression or death due to any cause, whichever is earlier, as assessed by the IRC per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis <10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline. Participants with response and without progression were censored at the last observation.
measure: Time to Response (TTR) as Assessed by the Investigator
time frame: From the date of randomization up to the date of first documented CR or PR (Up to approximately 2 years)
description: TTR was defined as the time from date of randomization to date of first documented CR or PR for responders, as assessed by the Investigator per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis <10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline. Only responders were analyzed for this outcome measure.
measure: TTR as Assessed by the IRC Per RECIST v1.1
time frame: From the date of randomization up to the date of first documented CR or PR (Up to approximately 2 years)
description: TTR was defined as the time from date of randomization to date of first documented CR or PR for responders, as assessed by the IRC per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis <10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline. Only responders were analyzed for this outcome measure.
measure: PFS as Determined by Investigator
time frame: From the date of randomization to the date of first documentation of disease progression or death due to any cause (Up to approximately 2 years)
description: PFS was defined as the time from date of randomization to the date of first documented disease progression as assessed by the investigator using RECIST v1.1, or date of death due to any cause, whichever occurred first. Disease progression was defined as ≥20% increase in sum of the diameter of target lesions, taking as reference the smallest sum diameter recorded since the treatment started. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm or the appearance of 1 or more new lesions. No progression or death by data cutoff date was censored at the last adequate assessment date.
measure: Change From Baseline in Health-Related Quality of Life (HRQOL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30 Subscales Scores
time frame: Cycle 2 Day 1 and Cycle 3 Day 1
description: EORTC-QLQ-C30 is the European Organization for Research and Treatment of Cancer - Quality of Life Questionnaire - Core Questionnaire. For EORTC QLQ-C30, subscales of physical functioning, pain, and appetite loss were assessed. These had 4 response levels (not at all, a little, quite a bit, and very much). For functional scales, higher scores=better QOL (positive change from Baseline=improvement). For symptom scales, lower scores=better QOL (negative change from Baseline=improvement). Using linear transformation, raw scores were standardized, so that scores ranged from 0 to 100.
measure: Change From Baseline in HRQOL Based on: Quality of Life Questionnaire - Cholangiocarcinoma and Gallbladder Cancer Module (QLQ-BIL21)
time frame: Cycle 2 Day 1 and Cycle 3 Day 1
description: For HRQOL based on QLQ-BIL21, subscales of eating symptoms and pain symptoms were assessed. Each item is a 4-point Likert scale. There are 4 response levels (not at all, a little, quite a bit, and very much). Raw scores are converted into scale scores ranging from 0 to 100. For symptom scales, lower scores=better QOL (negative change from Baseline=improvement).
measure: Percentage of Participants With Change Based on HRQOL: Patient Global Impression of Change (PGI-C)
time frame: Cycle 2 Day 1 and Cycle 3 Day 1
description: The PGI-C is a self-rated evaluative instrument for assessment across 3 domains (physical function, appetite loss, and pain). The PGI-C is measured using a 7-point Likert scale, with 6= very much better, 5= moderately better, 4= a little better, 3= no change, 2= a little worse, 1= moderately worse, and 0= very much worse. A lower score indicates a worse outcome. Percentages are rounded off to whole number at the nearest decimal.
measure: Percentage of Participants With Severity Based on HRQOL: Patient Global Impression of Severity (PGI-S)
time frame: Cycle 2 Day 1 and Cycle 3 Day 1
description: The anchor-based questionnaire PGI-S contains the following 3 items (the severity of the physical functioning decline over the past week, the severity of the appetite decrease over the past week, and the severity of the pain over the past week). The PGI-S was measured using the possible outcomes none, mild, moderate, severe, and very severe. Percentages are rounded off to whole number at the nearest decimal.
measure: Percentage of Participants With Each EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) Dimension Response
time frame: Cycle 3 Day 1
description: The EQ-5D-5L assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Percentages are rounded off to whole number at the nearest decimal.
measure: Change From Baseline in EQ-5D-5L Visual Analogue Scale (EQ-5D-5L VAS) Score
time frame: Cycle 3 Day 1
description: The EQ visual analogue scale records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled "The best health you can imagine" and "The worst health you can imagine." Responses are marked on a 0-100 scale with higher scores indicating higher health-related quality of life (i.e., better outcome).
measure: Maximum Observed Plasma Concentration (Cmax) of AG-120
time frame: Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)
description: Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.
measure: Time to Reach Maximal Plasma Concentration (Tmax) of AG-120
time frame: Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)
description: Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.
measure: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24)
time frame: Post-dose of Cycle 2 Day 1 (each cycle = 28 days)
description: Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.
measure: Area Under the Plasma Concentration-time Curve From Time Zero to 4 Hours (AUC0-4)
time frame: Post-dose of Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)
description: Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.
measure: Accumulation Ratio Based on AUC0-4 (Racc AUC0-4)
time frame: Post-dose Cycle 2 Day 1 (each cycle = 28 days)
description: Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.
measure: Accumulation Ratio Based on Cmax (Racc Cmax)
time frame: Post-dose Cycle 2 Day 1 (each cycle = 28 days)
description: Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.
measure: Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: B (Baseline Effect Value)
time frame: Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)
description: B is the Baseline Effect Value. Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.
measure: Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: AUEC0-4
time frame: Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)
description: AUEC0-4 is the area of the response curve from time point zero (predose) up to 4 hr postdose. Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.
measure: Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: %BAUEC0-4
time frame: Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)
description: %BAUEC0-4 is the percent inhibition for AUEC0-4. Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint.
measure: Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: Rtrough
time frame: Post-dose Cycle 2 Day 1 (each cycle = 28 days)
description: Rtrough is the observed response value at the end of a dosing interval. Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.
measure: Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: %BRtrough
time frame: Post-dose Cycle 2 Day 1 (each cycle = 28 days)
description: %BRtrough is the percent inhibition for Rtrough. Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint.
arm group label: AG-120
arm group type: Active Comparator
description: Participants received AG-120 500 mg, tablet, orally, once a day (QD) in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 45 months.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 7 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.
arm group label: After Cross over to AG-120
arm group type: Experimental
description: Participants who experienced disease progression and received placebo were allowed to cross over to receive AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle for up to approximately 32 months.
intervention type: Drug
intervention name: AG-120
description: Tablet administered orally
arm group label: AG-120
arm group label: After Cross over to AG-120
other name: Ivosidenib
intervention type: Drug
intervention name: Placebo
description: Tablet administered orally
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Affairs Servier Pharmaceuticals LLC
role: Study Chair
affiliation: Servier Pharmaceuticals, LLC
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country: France
country: Italy
country: Korea, Republic of
country: Spain
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Cholangiocarcinoma
mesh term: Ivosidenib
sharing ipd: Yes
ipd description: Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.
Access can be requested for all interventional clinical studies:
used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.
In addition, access can be requested for all interventional clinical studies in patients:
sponsored by Servier
with a first patient enrolled as of 1 January 2004 onwards
for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
ipd access criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
ipd url: https://clinicaltrials.servier.com/
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