<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/NCT03028103</url>
  </required_header>
  <id_info>
    <org_study_id>EZH-105</org_study_id>
    <nct_id>NCT03028103</nct_id>
  </id_info>
  <brief_title>Open-Label, Multicenter, Two-Part, Phase 1 Study to Characterize Effects of a Moderate CYP3A Inhibitor on PK of Tazemetostat, Effects of Tazemetostat on PK of CYP2C8 and CYP2C19 Substrates, and Effect of Increased Gastric pH on PK of Tazemetostat in B-cell Lymphoma or Advanced Solid Tumor Patients</brief_title>
  <official_title>An Open-Label, Multicenter, Two-Part, Phase 1 Study to Characterize the Effects of a Moderate CYP3A Inhibitor on the Pharmacokinetics of Tazemetostat (EPZ-6438) (Part A), the Effects of Tazemetostat on the Pharmacokinetics of CYP2C8 and CYP2C19 Substrates, and the Effect of Increased Gastric pH on the Pharmacokinetics of Tazemetostat (Part B) in Subjects With B-cell Lymphoma or Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Epizyme, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ipsen</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 1, open-label, two-part, safety, PK, and activity study designed to&#xD;
      characterize the DDI potential of tazemetostat. Tazemetostat will be taken orally BID&#xD;
      continuously in 28-day cycles in both study parts.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 27, 2017</start_date>
  <completion_date type="Actual">November 29, 2019</completion_date>
  <primary_completion_date type="Actual">October 31, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Part A: Effect of CYP3A Inhibition by Fluconazole on the PK of Tazemetostat (AUC0-t, AUC0-8)</measure>
    <time_frame>Days 15 and 19, 0 to 8 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part A: Cmax of Tazemetostat During Co-administration With Fluconazole</measure>
    <time_frame>Days 15 and 19, 0 to 8 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part B: The Potential of Tazemetostat to Inhibit or Induce CYP2C8 Using Repaglinide as a Probe Substrate (AUC0-t, AUC0-∞)</measure>
    <time_frame>Days 1 and 16, 0 to 8 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part B: Cmax of Repaglinide During Co-administration With Tazemetostat</measure>
    <time_frame>Days 1 and 16, 0 to 8 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part B: The Potential of Tazemetostat to Inhibit or Induce CYP2C19 Using Omeprazole as Probe a Substrate (AUC0-t, AUC0-∞)</measure>
    <time_frame>Days 1 and 16, 0 to 8 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part B: Cmax of Omeprazole During Co-administration With Tazemetostat</measure>
    <time_frame>Days 1 and 16, 0 to 8 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part B: Effect of Increased Gastric pH by Omeprazole on the PK of Tazemetostat (AUC0-t, AUC0-8)</measure>
    <time_frame>Days 16 and 19, 0 to 8 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part B: Cmax of Tazemetostat During Co-administration With Omeprazole</measure>
    <time_frame>Days 16 and 19, 0 to 8 hours post-dose</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of Treatment-emergent Adverse Events as a Measure of Safety</measure>
    <time_frame>From the first dose of study treatment until the earlier of either 30 days after the discontinuation of study treatment or until the initiation of subsequent anticancer therapy, up to 2 years.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: PK of Tazemetostat and Its Metabolites After Administration Alone and With Fluconazole (AUC0-t, AUC0-8)</measure>
    <time_frame>Days 15 and 19, 0 to 8 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Tmax of Tazemetostat After Administration Alone and With Fluconazole</measure>
    <time_frame>Days 15 and 19, 0 to 8 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: t1/2 of Tazemetostat After Administration Alone and With Fluconazole</measure>
    <time_frame>Days 15 and 19, 0 to 8 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Cmax of Tazemetostat Metabolites After Administration Alone and With Fluconazole</measure>
    <time_frame>Days 15 and 19, 0 to 8 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Tmax of Tazemetostat Metabolites After Administration Alone and With Fluconazole</measure>
    <time_frame>Days 15 and 19, 0 to 8 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: t1/2 of Tazemetostat Metabolites After Administration Alone and With Fluconazole</measure>
    <time_frame>Days 15 and 19, 0 to 8 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Exposure of Fluconazole After Administration of 400 mg Once Daily for 4 Days (AUC0-8)</measure>
    <time_frame>Day 19, 0 to 8 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Cmax of Fluconazole After Administration of 400mg Once Daily for 4 Days</measure>
    <time_frame>Day 19, 0 to 8 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Tmax of Fluconazole After Administration of 400mg Once Daily for 4 Days</measure>
    <time_frame>Day 19, 0 to 8 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Antitumor Activity of Tazemetostat Will be Assessed in Patients With Diffuse Large B-cell Lymphoma (DLBCL), Marginal Zone Lymphoma (MZL), Follicular Lymphoma (FL) or Advanced Solid Tumors .</measure>
    <time_frame>Within 28 days of Day 1, 8 weeks, 16 weeks, 24 weeks</time_frame>
    <description>Objective response rate (ORR: complete response [CR] or PR) and disease control rate (DCR: CR or PR, or stable disease lasting 24 weeks or longer from start of treatment with tazemetostat) using Lugano Classification for subjects with lymphoma, or Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for subjects with solid tumors.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Diffuse Large B Cell Lymphoma</condition>
  <condition>Primary Mediastinal Lymphoma</condition>
  <condition>Mantle Cell Lymphoma</condition>
  <condition>Advanced Solid Tumor</condition>
  <condition>Marginal Zone Lymphoma</condition>
  <arm_group>
    <arm_group_label>Part A and B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25.&#xD;
Part B: Subjects enrolled in Part B will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg on Day 1. Administration of tazemetostat 800 mg BID will begin on Day 2. On Day 16, subjects again will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg approximately 1 hour after the morning dose of tazemetostat. Subjects also will receive omeprazole 20 mg once daily in the morning on Days 16 through 19.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tazemetostat</intervention_name>
    <description>Tazemetostat is a selective oral small molecule inhibitor of EZH2</description>
    <arm_group_label>Part A and B</arm_group_label>
    <other_name>EPZ-6438, E7438</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluconazole</intervention_name>
    <description>200mg will be orally administered QD for 4 days in order to determine CYP3A4 inhibition when administered concomitantly with tazemetostat</description>
    <arm_group_label>Part A and B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Omeprazole</intervention_name>
    <description>Using omeprazole as a probe substrate, 20mg will be orally administered for a total of 5 days in order to determine the potential of tazemetostat to inhibit or induce CYP2C19. Omeprazole is also being used to determine the effect of increased gastric pH on metabolism of tazemetostat.</description>
    <arm_group_label>Part A and B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Repaglinide</intervention_name>
    <description>Using repaglinide as a probe substrate, 25mg will be orally administered for a total of 2 days in order to determine the potential of tazemetostat to inhibit or induce CYP2C8.</description>
    <arm_group_label>Part A and B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          1. Male or female ≥ 18 years of age at time of consent&#xD;
&#xD;
          2. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2&#xD;
&#xD;
          3. Has the ability to understand informed consent and provided signed written informed&#xD;
             consent&#xD;
&#xD;
             Must meet one of the following criteria:&#xD;
&#xD;
          4. Has histologically confirmed diffuse large B-cell lymphoma (DLBCL), primary&#xD;
             mediastinal B-cell lymphoma (PMBCL), marginal zone lymphoma (MZL), mantle cell&#xD;
             lymphoma (MCL) and have relapsed or refractory disease following at least two lines of&#xD;
             prior standard therapy, including alkylator/anthracycline (unless anthracycline-based&#xD;
             chemotherapy is contraindicated)/anti-CD20-based therapy (R-CHOP; rituximab,&#xD;
             doxorubicin, cyclophosphamide, vincristine, and prednisolone or prednisone, or&#xD;
             equivalent) AND must be considered unable to benefit from intensification treatment&#xD;
             with autologous hematopoietic stem cell transplantation (ASCT), as defined by meeting&#xD;
             at least one of the following criteria:&#xD;
&#xD;
               1. Relapsed following, or refractory to, previous ASCT&#xD;
&#xD;
               2. Did not achieve at least a partial response (PR) to a standard salvage regimen&#xD;
                  (e.g., R-ICE; rituximab, ifosfamide, carboplatin, etoposide, or R-DHAP;&#xD;
                  rituximab, dexamethasone, cytarabine, cisplatin)&#xD;
&#xD;
               3. Ineligible for intensification treatment due to age or significant comorbidity&#xD;
&#xD;
               4. Ineligible for intensification treatment due to failure to mobilize an acceptable&#xD;
                  number of hematopoietic stem cells&#xD;
&#xD;
               5. Refused intensification treatment and/or ASCT Note: Subjects with prior&#xD;
                  radiotherapy will be included; however, radiotherapy alone will not be considered&#xD;
                  a separate systemic treatment regimen.&#xD;
&#xD;
             Note: Subjects with prior radiotherapy will be included; however, radiotherapy alone&#xD;
             will not be considered a separate systemic treatment regimen.&#xD;
&#xD;
             OR&#xD;
&#xD;
          5. Has histologically confirmed FL, all grades. Subjects must have relapsed/refractory&#xD;
             disease following at least 2 standard lines of systemic therapy, including at least 1&#xD;
             anti-CD20-based regimen (eg, rituximab), as well as alkalating agents (eg,&#xD;
             cyclophosphamide or bendamustine), and have no curative option with other available&#xD;
             therapies OR have a contra-indication to their use. Subjects with prior ASCT may be&#xD;
             included. Transformed disease is permitted.&#xD;
&#xD;
             Note: Subjects with prior radiotherapy will be included; however, radiotherapy alone&#xD;
             will not be considered a separate systemic treatment regimen.&#xD;
&#xD;
             OR&#xD;
&#xD;
          6. Histologically and/or cytologically confirmed advanced or metastatic solid tumor that&#xD;
             has progressed after treatment with approved therapies or for which there are no&#xD;
             standard therapies available&#xD;
&#xD;
          7. Must have evaluable or measurable disease&#xD;
&#xD;
          8. Has all prior treatment (i.e., chemotherapy, immunotherapy, radiotherapy) related&#xD;
             clinically significant toxicities resolve to ≤ Grade 1 per NCI CTCAE, Version 4.03 or&#xD;
             are clinically stable and not clinically significant, at time of consent&#xD;
&#xD;
          9. Time required between the last dose of the latest therapy and the first dose of study&#xD;
             drug:&#xD;
&#xD;
               1. Chemotherapy: cytotoxic At least 21 days&#xD;
&#xD;
               2. Chemotherapy: nitrosoureas At least 6 weeks&#xD;
&#xD;
               3. Chemotherapy: non-cytotoxic (e.g., small molecule inhibitor) At least 14 days&#xD;
&#xD;
               4. Monoclonal antibody (ies) At least 28 days&#xD;
&#xD;
               5. Non-antibody immunotherapy (e.g., tumor vaccine) At least 42 days&#xD;
&#xD;
               6. At least 14 days for stereotactic radiosurgery&#xD;
&#xD;
               7. At least 12 weeks for craniospinal, ≥50% radiation of pelvis, or total body&#xD;
                  irradiation prior to first dose of study drug&#xD;
&#xD;
               8. Autologous hematopoietic cell infusion after high dose therapy At least 60 days&#xD;
&#xD;
               9. Hematopoietic growth factor At least 14 days&#xD;
&#xD;
         10. Has adequate hematologic (bone marrow [BM] and coagulation factors), renal and hepatic&#xD;
             function&#xD;
&#xD;
               1. Hemoglobin ≥9 g/dL&#xD;
&#xD;
               2. Platelets ≥75,000/mm3 (≥75 × 10^9/L)&#xD;
&#xD;
               3. ANC: for patients with lymphoma ≥750/mm3 (≥0.75 × 10^9/L), for patients with&#xD;
                  advanced solid tumors ≥1,000/mm3 (≥1.0 × 10^9/L),&#xD;
&#xD;
               4. PT &lt;1.5 ULN&#xD;
&#xD;
               5. PTT &lt;1.5 ULN&#xD;
&#xD;
               6. eGFR ≥ 50 mL/min/1.73 m2&#xD;
&#xD;
               7. Conjugated bilirubin &lt;1.5 × ULN&#xD;
&#xD;
               8. AST &lt;3 × ULN&#xD;
&#xD;
               9. ALT &lt;3 × ULN&#xD;
&#xD;
             NOTE: Laboratory results obtained during screening should be used to determine&#xD;
             eligibility criteria. In situations where laboratory results are outside the permitted&#xD;
             range, the investigator may retest the subject and the subsequent within range&#xD;
             screening result may be used to determine the subject's eligibility.&#xD;
&#xD;
         11. Has a QT interval corrected by Fridericia's formula (QTcF) ≤480 msec&#xD;
&#xD;
         12. Subjects with a history of Hepatitis B or C are eligible on the condition that&#xD;
             subjects have adequate liver function as defined by the protocol and are hepatitis B&#xD;
             surface antigen negative and/or have undetectable HCV RNA.&#xD;
&#xD;
         13. Male subjects must refrain from donating sperm starting at the planned first dose of&#xD;
             investigational product (IP) until 30 days following the last dose of IP&#xD;
&#xD;
         14. Male subjects with a female partner of childbearing potential must:&#xD;
&#xD;
               1. Be vasectomized, or&#xD;
&#xD;
               2. Remain abstinent or use a condom as defined in Section 8.3.8.4.2, starting at the&#xD;
                  planned first dose of IP until 30 days following the last dose of IP. The&#xD;
                  reliability of sexual abstinence should be evaluated in relation to the duration&#xD;
                  of the clinical trial and the preferred and usual lifestyle of the subject.&#xD;
                  Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, or post-ovulation&#xD;
                  methods) and withdrawal are not acceptable methods of contraception.&#xD;
&#xD;
         15. Female partners of male subjects who are of childbearing potential must also adhere to&#xD;
             one of the following:&#xD;
&#xD;
               1. Placement of an intrauterine device or intrauterine system.&#xD;
&#xD;
               2. Established use of oral, injected, or implanted hormonal methods of contraception&#xD;
                  or use of a barrier method of contraception.&#xD;
&#xD;
               3. Progesterone only oral contraception, where inhibition of ovulation is not the&#xD;
                  primary mode of action.&#xD;
&#xD;
         16. Women of childbearing potential or female partners of male subjects must abide by the&#xD;
             contraception measures defined by the protocol&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Is pregnant or nursing&#xD;
&#xD;
          2. Has active central nervous system (CNS) or leptomeningeal metastasis&#xD;
&#xD;
          3. Has had a prior malignancy other than the malignancies under study Exception: Subject&#xD;
             who has been disease-free for 3 years, or a subject with a history of a completely&#xD;
             resected non-melanoma skin cancer or successfully treated in situ carcinoma are&#xD;
             eligible.&#xD;
&#xD;
          4. Has thrombocytopenia, neutropenia, or anemia of Grade ≥3 (per CTCAE 4.03 criteria) and&#xD;
             any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS).&#xD;
&#xD;
             NOTE: Bone marrow aspirate/biopsy will be conducted following abnormal peripheral&#xD;
             blood smear morphology assessment conducted by the local laboratory. Cytogenetic&#xD;
             testing and DNA sequencing will be conducted following an abnormal result of bone&#xD;
             marrow aspirate/biopsy.&#xD;
&#xD;
          5. Has a prior history of T-LBL/T-ALL.&#xD;
&#xD;
          6. Has had major surgery within 3 weeks prior to enrollment NOTE: Minor surgery (e.g.,&#xD;
             minor biopsy, central venous catheter placement) is permitted within 3 weeks prior to&#xD;
             enrollment.&#xD;
&#xD;
          7. Is unwilling to exclude grapefruit juice, Seville oranges, and grapefruit from the&#xD;
             diet and all foods that contain those fruits from time of enrollment to while on study&#xD;
&#xD;
          8. Has cardiovascular impairment, history of congestive heart failure greater than NYHA&#xD;
             Class II uncontrolled arterial hypertension, unstable angina, myocardial infarction,&#xD;
             or stroke within 6 months prior to the planned first dose of tazemetostat; or&#xD;
             ventricular cardiac arrhythmia requiring medical treatment&#xD;
&#xD;
          9. Subjects taking medications that are known potent or moderate inducers/ inhibitors of&#xD;
             CYP3A4 (including St. John's Wort)&#xD;
&#xD;
         10. Has an active infection or recent history (&lt;30 days before study drug administration)&#xD;
             requiring systemic treatment&#xD;
&#xD;
         11. Is immunocompromised, including subjects with known human immunodeficiency virus (HIV)&#xD;
             infection&#xD;
&#xD;
         12. Has known hypersensitivity to any of the components of IP.&#xD;
&#xD;
         13. Is unable to take oral medications, has a history of surgery that would interfere with&#xD;
             the administration or absorption of oral medication, has malabsorption syndrome or any&#xD;
             other uncontrolled gastrointestinal condition (e.g., nausea, diarrhea or vomiting)&#xD;
             that might impair the bioavailability of IP&#xD;
&#xD;
         14. Has an uncontrolled intercurrent illness including, but not limited to, uncontrolled&#xD;
             infection, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements.&#xD;
&#xD;
         15. Is unwilling to adhere to contraception criteria from time of enrollment in study to&#xD;
             at least 30 days after last dose of IP.&#xD;
&#xD;
         16. A history of bleeding (i.e., hemoptysis, hematuria, gastrointestinal blood loss,&#xD;
             epistaxis, or others with greater than Grade 1 according to NCI CTCAE Version 4.03)&#xD;
             within 1 month prior to beginning therapy or any clinical indications of current&#xD;
             active bleeding.&#xD;
&#xD;
         17. Clinical history, current alcohol (ethanol), or illicit drug use which, in the&#xD;
             judgment of the investigator, will interfere with the subject's ability to comply with&#xD;
             the dosing schedule and protocol-specified evaluations.&#xD;
&#xD;
         18. Regular alcohol consumption averaging more than seven drinks/week for women and 14&#xD;
             drinks/week for men within 6 months of screening.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Arizona Cancer Center</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85719</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Moffitt Cancer Center</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>December 19, 2016</study_first_submitted>
  <study_first_submitted_qc>January 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 23, 2017</study_first_posted>
  <results_first_submitted>December 7, 2020</results_first_submitted>
  <results_first_submitted_qc>March 23, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">April 19, 2021</results_first_posted>
  <last_update_submitted>June 23, 2023</last_update_submitted>
  <last_update_submitted_qc>June 23, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 26, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, B-Cell</mesh_term>
    <mesh_term>Lymphoma, Mantle-Cell</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Repaglinide</mesh_term>
    <mesh_term>Fluconazole</mesh_term>
    <mesh_term>Omeprazole</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 28, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/03/NCT03028103/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Part A</title>
          <description>Subjects enrolled in Part A received treatment with oral tazemetostat tablets 400 mg twice daily for 24 days beginning on Day 1. Blood samples for the analysis of plasma tazemetostat and its metabolites concentrations were collected predose and over 8 hours after the morning dose of tazemetostat on Day 15. Subjects received fluconazole 400 mg once daily for 4 days starting on Day 16. On Day 19, blood samples for the analysis of plasma tazemetostat, its metabolites, and fluconazole were collected predose and over 8 hours after the morning tazemetostat dose. Tazemetostat 400 mg twice daily continued through Day 24. Subjects then received tazemetostat 800 mg twice daily starting on Day 25.</description>
        </group>
        <group group_id="P2">
          <title>Part B</title>
          <description>Subjects enrolled in Part B received single oral doses of repaglinide 0.25 mg and omeprazole 20 mg on Day 1. Administration of tazemetostat 800 mg twice daily began on Day 2. On Day 16, subjects again received single oral doses of repaglinide 0.25 mg and omeprazole 20 mg approximately 1 hour after the morning dose of tazemetostat. Subjects also received omeprazole 20 mg once daily in the morning on Days 16 through 19. Blood samples for analysis of plasma repaglinide, repaglinide metabolites, omeprazole, 5-OH-omeprazole, and omeprazole sulfone were collected predose and over 7 hours after administration on Day 1 and Day 16. Blood samples for analysis of plasma tazemetostat and metabolites were collected over 8 hours after administration of the morning dose on Day 16 and Day 19.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Part A</title>
          <description>Subjects enrolled in Part A received treatment with oral tazemetostat tablets 400 mg twice daily for 24 days beginning on Day 1. Blood samples for the analysis of plasma tazemetostat and its metabolites concentrations were collected predose and over 8 hours after the morning dose of tazemetostat on Day 15. Subjects received fluconazole 400 mg once daily for 4 days starting on Day 16. On Day 19, blood samples for the analysis of plasma tazemetostat, its metabolites, and fluconazole were collected predose and over 8 hours after the morning tazemetostat dose. Tazemetostat 400 mg twice daily continued through Day 24. Subjects then received tazemetostat 800 mg twice daily starting on Day 25.</description>
        </group>
        <group group_id="B2">
          <title>Part B</title>
          <description>Subjects enrolled in Part B received single oral doses of repaglinide 0.25 mg and omeprazole 20 mg on Day 1. Administration of tazemetostat 800 mg twice daily began on Day 2. On Day 16, subjects again received single oral doses of repaglinide 0.25 mg and omeprazole 20 mg approximately 1 hour after the morning dose of tazemetostat. Subjects also received omeprazole 20 mg once daily in the morning on Days 16 through 19. Blood samples for analysis of plasma repaglinide, repaglinide metabolites, omeprazole, 5-OH-omeprazole, and omeprazole sulfone were collected predose and over 7 hours after administration on Day 1 and Day 16. Blood samples for analysis of plasma tazemetostat and metabolites were collected over 8 hours after administration of the morning dose on Day 16 and Day 19.</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="16"/>
            <count group_id="B2" value="16"/>
            <count group_id="B3" value="32"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="62.9" spread="15.10"/>
                    <measurement group_id="B2" value="48.8" spread="17.75"/>
                    <measurement group_id="B3" value="55.8" spread="17.73"/>
                  </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="10"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline Disease Characteristics and Prior Therapies</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Lymphoma</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Advanced Solid tumors</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stage at diagnosis: I</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stage at diagnosis: II</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stage at diagnosis: III</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stage at diagnosis: IV</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stage at diagnosis: Unknown</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Progressive disease prior to study entry</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Part A: Effect of CYP3A Inhibition by Fluconazole on the PK of Tazemetostat (AUC0-t, AUC0-8)</title>
        <time_frame>Days 15 and 19, 0 to 8 hours post-dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Part A</title>
            <description>Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25.</description>
          </group>
        </group_list>
        <measure>
          <title>Part A: Effect of CYP3A Inhibition by Fluconazole on the PK of Tazemetostat (AUC0-t, AUC0-8)</title>
          <units>h*ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ-6438</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1340" spread="1180"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ-6438</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4100" spread="2680"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Part A: Cmax of Tazemetostat During Co-administration With Fluconazole</title>
        <time_frame>Days 15 and 19, 0 to 8 hours post-dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Part A</title>
            <description>Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25.</description>
          </group>
        </group_list>
        <measure>
          <title>Part A: Cmax of Tazemetostat During Co-administration With Fluconazole</title>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ-6438</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="426" spread="337"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ-6438</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="968" spread="801"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Part B: The Potential of Tazemetostat to Inhibit or Induce CYP2C8 Using Repaglinide as a Probe Substrate (AUC0-t, AUC0-∞)</title>
        <time_frame>Days 1 and 16, 0 to 8 hours post-dose</time_frame>
        <population>In Part B, 13 subjects completed taking omeprazole and repaglinide on Day 1, with tazemetostat on Day 16 and 11 subjects completed taking tazemetostat alone on Day 19.</population>
        <group_list>
          <group group_id="O1">
            <title>Part B</title>
            <description>Part B: Subjects enrolled in Part B will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg on Day 1. Administration of tazemetostat 800 mg BID will begin on Day 2. On Day 16, subjects again will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg approximately 1 hour after the morning dose of tazemetostat. Subjects also will receive omeprazole 20 mg once daily in the morning on Days 16 through 19.</description>
          </group>
        </group_list>
        <measure>
          <title>Part B: The Potential of Tazemetostat to Inhibit or Induce CYP2C8 Using Repaglinide as a Probe Substrate (AUC0-t, AUC0-∞)</title>
          <population>In Part B, 13 subjects completed taking omeprazole and repaglinide on Day 1, with tazemetostat on Day 16 and 11 subjects completed taking tazemetostat alone on Day 19.</population>
          <units>h*ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Part: B; Day 1; Treatment: Repaglinide Alone; Analyte: Repaglinide - AUC(0-t)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.16" spread="13.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: B; Day 16; Treatment: Repaglinide with Tazemetostat; Analyte: Repaglinide - AUC(0-t)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.7" spread="15.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: B; Day 1; Treatment: Repaglinide Alone; Analyte: Repaglinide - AUC(0-∞)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.7" spread="19.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: B; Day 16; Treatment: Repaglinide with Tazemetostat; Analyte: Repaglinide - AUC(0-∞)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17" spread="15.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Part B: Cmax of Repaglinide During Co-administration With Tazemetostat</title>
        <time_frame>Days 1 and 16, 0 to 8 hours post-dose</time_frame>
        <population>In Part B, 13 subjects completed taking omeprazole and repaglinide on Day 1, with tazemetostat on Day 16 and 11 subjects completed taking tazemetostat alone on Day 19.</population>
        <group_list>
          <group group_id="O1">
            <title>Part B</title>
            <description>Part B: Subjects enrolled in Part B will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg on Day 1. Administration of tazemetostat 800 mg BID will begin on Day 2. On Day 16, subjects again will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg approximately 1 hour after the morning dose of tazemetostat. Subjects also will receive omeprazole 20 mg once daily in the morning on Days 16 through 19.</description>
          </group>
        </group_list>
        <measure>
          <title>Part B: Cmax of Repaglinide During Co-administration With Tazemetostat</title>
          <population>In Part B, 13 subjects completed taking omeprazole and repaglinide on Day 1, with tazemetostat on Day 16 and 11 subjects completed taking tazemetostat alone on Day 19.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Part: B; Day 1; Treatment: Repaglinide Alone; Analyte: Repaglinide</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.14" spread="8.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: B; Day 16; Treatment: Repaglinide with Tazemetostat; Analyte: Repaglinide</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.75" spread="8.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Part B: The Potential of Tazemetostat to Inhibit or Induce CYP2C19 Using Omeprazole as Probe a Substrate (AUC0-t, AUC0-∞)</title>
        <time_frame>Days 1 and 16, 0 to 8 hours post-dose</time_frame>
        <population>In Part B, 13 subjects completed taking omeprazole and repaglinide on Day 1, with tazemetostat on Day 16 and 11 subjects completed taking tazemetostat alone on Day 19.</population>
        <group_list>
          <group group_id="O1">
            <title>Part B</title>
            <description>Part B: Subjects enrolled in Part B will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg on Day 1. Administration of tazemetostat 800 mg BID will begin on Day 2. On Day 16, subjects again will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg approximately 1 hour after the morning dose of tazemetostat. Subjects also will receive omeprazole 20 mg once daily in the morning on Days 16 through 19.</description>
          </group>
        </group_list>
        <measure>
          <title>Part B: The Potential of Tazemetostat to Inhibit or Induce CYP2C19 Using Omeprazole as Probe a Substrate (AUC0-t, AUC0-∞)</title>
          <population>In Part B, 13 subjects completed taking omeprazole and repaglinide on Day 1, with tazemetostat on Day 16 and 11 subjects completed taking tazemetostat alone on Day 19.</population>
          <units>h*ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Part: B; Day 1; Treatment: Omeprazole Alone; Analyte: Omeprazole - AUC(0-t)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="600" spread="1600"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: B; Day 16; Treatment: Omeprazole with Tazemetostat; Analyte: Omeprazole - AUC(0-t)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="480" spread="837"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: B; Day 1; Treatment: Omeprazole Alone; Analyte: Omeprazole - AUC(0-∞)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="672" spread="463"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: B; Day 16; Treatment: Omeprazole with Tazemetostat; Analyte: Omeprazole - AUC(0-∞)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1120" spread="1530"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Part B: Cmax of Omeprazole During Co-administration With Tazemetostat</title>
        <time_frame>Days 1 and 16, 0 to 8 hours post-dose</time_frame>
        <population>In Part B, 13 subjects completed taking omeprazole and repaglinide on Day 1, with tazemetostat on Day 16 and 11 subjects completed taking tazemetostat alone on Day 19.</population>
        <group_list>
          <group group_id="O1">
            <title>Part B</title>
            <description>Part B: Subjects enrolled in Part B will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg on Day 1. Administration of tazemetostat 800 mg BID will begin on Day 2. On Day 16, subjects again will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg approximately 1 hour after the morning dose of tazemetostat. Subjects also will receive omeprazole 20 mg once daily in the morning on Days 16 through 19.</description>
          </group>
        </group_list>
        <measure>
          <title>Part B: Cmax of Omeprazole During Co-administration With Tazemetostat</title>
          <population>In Part B, 13 subjects completed taking omeprazole and repaglinide on Day 1, with tazemetostat on Day 16 and 11 subjects completed taking tazemetostat alone on Day 19.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Part: B; Day 1; Treatment: Omeprazole Alone; Analyte: Omeprazole</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="253" spread="462"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: B; Day 16; Treatment: Omeprazole with Tazemetostat; Analyte: Omeprazole</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="207" spread="275"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Part B: Effect of Increased Gastric pH by Omeprazole on the PK of Tazemetostat (AUC0-t, AUC0-8)</title>
        <time_frame>Days 16 and 19, 0 to 8 hours post-dose</time_frame>
        <population>In Part B, 13 subjects completed taking omeprazole and repaglinide on Day 1, with tazemetostat on Day 16 and 11 subjects completed taking tazemetostat alone on Day 19.</population>
        <group_list>
          <group group_id="O1">
            <title>Part B</title>
            <description>Part B: Subjects enrolled in Part B will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg on Day 1. Administration of tazemetostat 800 mg BID will begin on Day 2. On Day 16, subjects again will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg approximately 1 hour after the morning dose of tazemetostat. Subjects also will receive omeprazole 20 mg once daily in the morning on Days 16 through 19.</description>
          </group>
        </group_list>
        <measure>
          <title>Part B: Effect of Increased Gastric pH by Omeprazole on the PK of Tazemetostat (AUC0-t, AUC0-8)</title>
          <population>In Part B, 13 subjects completed taking omeprazole and repaglinide on Day 1, with tazemetostat on Day 16 and 11 subjects completed taking tazemetostat alone on Day 19.</population>
          <units>h*ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Part: B; Day 16; Treatment: Omeprazole with Tazemetostat; Analyte: EPZ-6438 - AUC(0-t)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1780" spread="2010"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: B; Day 19; Treatment: Tazemetostat Alone; Analyte: EPZ-6438 - AUC(0-t)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2150" spread="1030"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Part B: Cmax of Tazemetostat During Co-administration With Omeprazole</title>
        <time_frame>Days 16 and 19, 0 to 8 hours post-dose</time_frame>
        <population>In Part B, 13 subjects completed taking omeprazole and repaglinide on Day 1, with tazemetostat on Day 16 and 11 subjects completed taking tazemetostat alone on Day 19.</population>
        <group_list>
          <group group_id="O1">
            <title>Part B</title>
            <description>Part B: Subjects enrolled in Part B will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg on Day 1. Administration of tazemetostat 800 mg BID will begin on Day 2. On Day 16, subjects again will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg approximately 1 hour after the morning dose of tazemetostat. Subjects also will receive omeprazole 20 mg once daily in the morning on Days 16 through 19.</description>
          </group>
        </group_list>
        <measure>
          <title>Part B: Cmax of Tazemetostat During Co-administration With Omeprazole</title>
          <population>In Part B, 13 subjects completed taking omeprazole and repaglinide on Day 1, with tazemetostat on Day 16 and 11 subjects completed taking tazemetostat alone on Day 19.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Part: B; Day 16; Treatment: Omeprazole with Tazemetostat; Analyte: EPZ-6438</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="521" spread="627"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: B; Day 19; Treatment: Tazemetostat Alone; Analyte: EPZ-6438</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="641" spread="404"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Treatment-emergent Adverse Events as a Measure of Safety</title>
        <time_frame>From the first dose of study treatment until the earlier of either 30 days after the discontinuation of study treatment or until the initiation of subsequent anticancer therapy, up to 2 years.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Part A</title>
            <description>Subjects enrolled in Part A received treatment with oral tazemetostat tablets 400 mg twice daily for 24 days beginning on Day 1. Blood samples for the analysis of plasma tazemetostat and its metabolites concentrations were collected predose and over 8 hours after the morning dose of tazemetostat on Day 15. Subjects received fluconazole 400 mg once daily for 4 days starting on Day 16. On Day 19, blood samples for the analysis of plasma tazemetostat, its metabolites, and fluconazole were collected predose and over 8 hours after the morning tazemetostat dose. Tazemetostat 400 mg twice daily continued through Day 24. Subjects then received tazemetostat 800 mg twice daily starting on Day 25.</description>
          </group>
          <group group_id="O2">
            <title>Part B</title>
            <description>Subjects enrolled in Part B received single oral doses of repaglinide 0.25 mg and omeprazole 20 mg on Day 1. Administration of tazemetostat 800 mg twice daily began on Day 2. On Day 16, subjects again received single oral doses of repaglinide 0.25 mg and omeprazole 20 mg approximately 1 hour after the morning dose of tazemetostat. Subjects also received omeprazole 20 mg once daily in the morning on Days 16 through 19. Blood samples for analysis of plasma repaglinide, repaglinide metabolites, omeprazole, 5-OH-omeprazole, and omeprazole sulfone were collected predose and over 7 hours after administration on Day 1 and Day 16. Blood samples for analysis of plasma tazemetostat and metabolites were collected over 8 hours after administration of the morning dose on Day 16 and Day 19.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Treatment-emergent Adverse Events as a Measure of Safety</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any TEAE Grade 3 or 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any Treatment-Related TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any Treatment-Related TEAE Grade 3 or 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any TEAE Leading to Dose Reduction</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any TEAE Leading to Study Drug Interruption</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any TEAE Leading to Study Drug Discontinuation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any TESAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any Treatment-Related TESAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any Protocol Defined AE of Special Interest</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part A: PK of Tazemetostat and Its Metabolites After Administration Alone and With Fluconazole (AUC0-t, AUC0-8)</title>
        <time_frame>Days 15 and 19, 0 to 8 hours post-dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Part A</title>
            <description>Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25.</description>
          </group>
        </group_list>
        <measure>
          <title>Part A: PK of Tazemetostat and Its Metabolites After Administration Alone and With Fluconazole (AUC0-t, AUC0-8)</title>
          <units>h*ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ-6930 (ER-897387)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2590" spread="1200"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ-6930 (ER-897387)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2860" spread="1600"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ006931</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="770" spread="630"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ006931</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="921" spread="780"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ034163</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="276" spread="415"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ034163</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="295" spread="430"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part A: Tmax of Tazemetostat After Administration Alone and With Fluconazole</title>
        <time_frame>Days 15 and 19, 0 to 8 hours post-dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Part A</title>
            <description>Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25.</description>
          </group>
        </group_list>
        <measure>
          <title>Part A: Tmax of Tazemetostat After Administration Alone and With Fluconazole</title>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ-6438</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.13" spread="0.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ-6438</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2" spread="0.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part A: t1/2 of Tazemetostat After Administration Alone and With Fluconazole</title>
        <time_frame>Days 15 and 19, 0 to 8 hours post-dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Part A</title>
            <description>Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25.</description>
          </group>
        </group_list>
        <measure>
          <title>Part A: t1/2 of Tazemetostat After Administration Alone and With Fluconazole</title>
          <units>hours</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ-6438</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.88" spread="0.491"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ-6438</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.56" spread="0.453"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part A: Cmax of Tazemetostat Metabolites After Administration Alone and With Fluconazole</title>
        <time_frame>Days 15 and 19, 0 to 8 hours post-dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Part A</title>
            <description>Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25.</description>
          </group>
        </group_list>
        <measure>
          <title>Part A: Cmax of Tazemetostat Metabolites After Administration Alone and With Fluconazole</title>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ-6930 (ER-897387)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="629" spread="270"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ-6930 (ER-897387)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="548" spread="288"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ006931</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="166" spread="105"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ006931</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="167" spread="153"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ034163</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46" spread="56.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ034163</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.1" spread="61.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part A: Tmax of Tazemetostat Metabolites After Administration Alone and With Fluconazole</title>
        <time_frame>Days 15 and 19, 0 to 8 hours post-dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Part A</title>
            <description>Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25.</description>
          </group>
        </group_list>
        <measure>
          <title>Part A: Tmax of Tazemetostat Metabolites After Administration Alone and With Fluconazole</title>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ-6930 (ER-897387)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.01" spread="0.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ-6930 (ER-897387)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.02" spread="0.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ006931</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.01" spread="0.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ006931</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.47" spread="0.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ034163</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.02" spread="1.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ034163</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.02" spread="1.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part A: t1/2 of Tazemetostat Metabolites After Administration Alone and With Fluconazole</title>
        <time_frame>Days 15 and 19, 0 to 8 hours post-dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Part A</title>
            <description>Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25.</description>
          </group>
        </group_list>
        <measure>
          <title>Part A: t1/2 of Tazemetostat Metabolites After Administration Alone and With Fluconazole</title>
          <units>hours</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ-6930 (ER-897387)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.89" spread="0.358"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ-6930 (ER-897387)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.92" spread="0.621"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ006931</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.24" spread="0.565"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part A: Exposure of Fluconazole After Administration of 400 mg Once Daily for 4 Days (AUC0-8)</title>
        <time_frame>Day 19, 0 to 8 hours post-dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Part A</title>
            <description>Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25.</description>
          </group>
        </group_list>
        <measure>
          <title>Part A: Exposure of Fluconazole After Administration of 400 mg Once Daily for 4 Days (AUC0-8)</title>
          <units>h*ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="170000" spread="48300"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part A: Cmax of Fluconazole After Administration of 400mg Once Daily for 4 Days</title>
        <time_frame>Day 19, 0 to 8 hours post-dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Part A</title>
            <description>Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25.</description>
          </group>
        </group_list>
        <measure>
          <title>Part A: Cmax of Fluconazole After Administration of 400mg Once Daily for 4 Days</title>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25900" spread="6500"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part A: Tmax of Fluconazole After Administration of 400mg Once Daily for 4 Days</title>
        <time_frame>Day 19, 0 to 8 hours post-dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Part A</title>
            <description>Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25.</description>
          </group>
        </group_list>
        <measure>
          <title>Part A: Tmax of Fluconazole After Administration of 400mg Once Daily for 4 Days</title>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.48" spread="1.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Antitumor Activity of Tazemetostat Will be Assessed in Patients With Diffuse Large B-cell Lymphoma (DLBCL), Marginal Zone Lymphoma (MZL), Follicular Lymphoma (FL) or Advanced Solid Tumors .</title>
        <description>Objective response rate (ORR: complete response [CR] or PR) and disease control rate (DCR: CR or PR, or stable disease lasting 24 weeks or longer from start of treatment with tazemetostat) using Lugano Classification for subjects with lymphoma, or Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for subjects with solid tumors.</description>
        <time_frame>Within 28 days of Day 1, 8 weeks, 16 weeks, 24 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Lymphoma</title>
            <description>Subjects with B-cell lymphomas</description>
          </group>
          <group group_id="O2">
            <title>Advanced Solid Tumors</title>
            <description>Subjects with Advanced Solid Tumors</description>
          </group>
        </group_list>
        <measure>
          <title>The Antitumor Activity of Tazemetostat Will be Assessed in Patients With Diffuse Large B-cell Lymphoma (DLBCL), Marginal Zone Lymphoma (MZL), Follicular Lymphoma (FL) or Advanced Solid Tumors .</title>
          <description>Objective response rate (ORR: complete response [CR] or PR) and disease control rate (DCR: CR or PR, or stable disease lasting 24 weeks or longer from start of treatment with tazemetostat) using Lugano Classification for subjects with lymphoma, or Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for subjects with solid tumors.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Complete response (CR)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Partial response (PR)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stable disease (SD)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Progressive disease (PD)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not evaluable, missing, or unknown</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Objective Response Rate (ORR)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Disease control rate (DCR) at 24 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of responders (achieving a CR or PR)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse Events were collected over a period of 2 years.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Part A</title>
          <description>Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25.</description>
        </group>
        <group group_id="E2">
          <title>Part B</title>
          <description>Part B: Subjects enrolled in Part B will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg on Day 1. Administration of tazemetostat 800 mg BID will begin on Day 2. On Day 16, subjects again will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg approximately 1 hour after the morning dose of tazemetostat. Subjects also will receive omeprazole 20 mg once daily in the morning on Days 16 through 19.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA v18.1</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="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="16"/>
              </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="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Faecal incontinence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Peritonitis bacterial</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Subdural haematoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Tumour pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA v18.1</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="12" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Stress cardiomyopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Diplopia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Ocular discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Photophobia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Macular oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Visual acuity reduced</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Eructation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Umbilical hernia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Mucosal inflammation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Face oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Generalised oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Seasonal allergy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Fungal skin infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Viral rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Osteomyelitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Otitis media</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Otitis media bacterial</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Arthropod bite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hip fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Incision site pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Blood calcium decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Blood immunoglobulin G decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Ejection fraction decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Haemoglobin decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Weight increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
              </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="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Groin pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Fracture pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Balance disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Brain compression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Neuropathy peripheral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Micturition urgency</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Testicular swelling</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </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="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Pulmonary pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Skin exfoliation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Skin fissures</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Skin lesion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Swelling face</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Ecchymosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Onychoclasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </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>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Kemly Calixte</name_or_title>
      <organization>Epizyme</organization>
      <phone>617-500-0608</phone>
      <email>kcalixte@epizyme.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/NCT03028103
org study id: EZH-105
nct id: NCT03028103
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase 1, open-label, two-part, safety, PK, and activity study designed to
      characterize the DDI potential of tazemetostat. Tazemetostat will be taken orally BID
      continuously in 28-day cycles in both study parts.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Part A: Effect of CYP3A Inhibition by Fluconazole on the PK of Tazemetostat (AUC0-t, AUC0-8)
time frame: Days 15 and 19, 0 to 8 hours post-dose
measure: Part A: Cmax of Tazemetostat During Co-administration With Fluconazole
time frame: Days 15 and 19, 0 to 8 hours post-dose
measure: Part B: The Potential of Tazemetostat to Inhibit or Induce CYP2C8 Using Repaglinide as a Probe Substrate (AUC0-t, AUC0-∞)
time frame: Days 1 and 16, 0 to 8 hours post-dose
measure: Part B: Cmax of Repaglinide During Co-administration With Tazemetostat
time frame: Days 1 and 16, 0 to 8 hours post-dose
measure: Part B: The Potential of Tazemetostat to Inhibit or Induce CYP2C19 Using Omeprazole as Probe a Substrate (AUC0-t, AUC0-∞)
time frame: Days 1 and 16, 0 to 8 hours post-dose
measure: Part B: Cmax of Omeprazole During Co-administration With Tazemetostat
time frame: Days 1 and 16, 0 to 8 hours post-dose
measure: Part B: Effect of Increased Gastric pH by Omeprazole on the PK of Tazemetostat (AUC0-t, AUC0-8)
time frame: Days 16 and 19, 0 to 8 hours post-dose
measure: Part B: Cmax of Tazemetostat During Co-administration With Omeprazole
time frame: Days 16 and 19, 0 to 8 hours post-dose
measure: Incidence of Treatment-emergent Adverse Events as a Measure of Safety
time frame: From the first dose of study treatment until the earlier of either 30 days after the discontinuation of study treatment or until the initiation of subsequent anticancer therapy, up to 2 years.
measure: Part A: PK of Tazemetostat and Its Metabolites After Administration Alone and With Fluconazole (AUC0-t, AUC0-8)
time frame: Days 15 and 19, 0 to 8 hours post-dose
measure: Part A: Tmax of Tazemetostat After Administration Alone and With Fluconazole
time frame: Days 15 and 19, 0 to 8 hours post-dose
measure: Part A: t1/2 of Tazemetostat After Administration Alone and With Fluconazole
time frame: Days 15 and 19, 0 to 8 hours post-dose
measure: Part A: Cmax of Tazemetostat Metabolites After Administration Alone and With Fluconazole
time frame: Days 15 and 19, 0 to 8 hours post-dose
measure: Part A: Tmax of Tazemetostat Metabolites After Administration Alone and With Fluconazole
time frame: Days 15 and 19, 0 to 8 hours post-dose
measure: Part A: t1/2 of Tazemetostat Metabolites After Administration Alone and With Fluconazole
time frame: Days 15 and 19, 0 to 8 hours post-dose
measure: Part A: Exposure of Fluconazole After Administration of 400 mg Once Daily for 4 Days (AUC0-8)
time frame: Day 19, 0 to 8 hours post-dose
measure: Part A: Cmax of Fluconazole After Administration of 400mg Once Daily for 4 Days
time frame: Day 19, 0 to 8 hours post-dose
measure: Part A: Tmax of Fluconazole After Administration of 400mg Once Daily for 4 Days
time frame: Day 19, 0 to 8 hours post-dose
measure: The Antitumor Activity of Tazemetostat Will be Assessed in Patients With Diffuse Large B-cell Lymphoma (DLBCL), Marginal Zone Lymphoma (MZL), Follicular Lymphoma (FL) or Advanced Solid Tumors .
time frame: Within 28 days of Day 1, 8 weeks, 16 weeks, 24 weeks
description: Objective response rate (ORR: complete response [CR] or PR) and disease control rate (DCR: CR or PR, or stable disease lasting 24 weeks or longer from start of treatment with tazemetostat) using Lugano Classification for subjects with lymphoma, or Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for subjects with solid tumors.
arm group label: Part A and B
arm group type: Experimental
description: Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25.
Part B: Subjects enrolled in Part B will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg on Day 1. Administration of tazemetostat 800 mg BID will begin on Day 2. On Day 16, subjects again will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg approximately 1 hour after the morning dose of tazemetostat. Subjects also will receive omeprazole 20 mg once daily in the morning on Days 16 through 19.
intervention type: Drug
intervention name: Tazemetostat
description: Tazemetostat is a selective oral small molecule inhibitor of EZH2
arm group label: Part A and B
other name: EPZ-6438, E7438
intervention type: Drug
intervention name: Fluconazole
description: 200mg will be orally administered QD for 4 days in order to determine CYP3A4 inhibition when administered concomitantly with tazemetostat
arm group label: Part A and B
intervention type: Drug
intervention name: Omeprazole
description: Using omeprazole as a probe substrate, 20mg will be orally administered for a total of 5 days in order to determine the potential of tazemetostat to inhibit or induce CYP2C19. Omeprazole is also being used to determine the effect of increased gastric pH on metabolism of tazemetostat.
arm group label: Part A and B
intervention type: Drug
intervention name: Repaglinide
description: Using repaglinide as a probe substrate, 25mg will be orally administered for a total of 2 days in order to determine the potential of tazemetostat to inhibit or induce CYP2C8.
arm group label: Part A and B
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, B-Cell
mesh term: Lymphoma, Mantle-Cell
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Repaglinide
mesh term: Fluconazole
mesh term: Omeprazole
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 