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This is a multicenter, single-arm, open-label, Phase 1 study to assess the tolerability, safety, pharmacokinetics, and preliminary anti-tumor activity of tazemetostat in participants with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tazemetostat 800 mg | Experimental | Participants will receive oral tazemetostat at a starting dose of 800 milligrams (mg) as a single dose (Cycle 0) and 800 mg twice a day as continuous dosing (Cycle 1 and later) (Cycle 0 duration=4 days) (Cycle 1 and later duration= 28 days). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tazemetostat | Drug | Tazemetostat tablets. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose-limiting Toxicities (DLTs) | DLTs as per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) were defined as: 1) Grade 4 neutropenia for greater than (>) 7 days; 2) greater than or equal to (>=) Grade 3 febrile neutropenia; 3) Grade 4 thrombocytopenia and Grade 3 thrombocytopenia with bleeding; 4) Grade 4 anemia or anemia requiring erythrocyte transfusion; 5) >=Grade 3 nausea, vomiting, or diarrhea that persisted >7 days despite maximal medical therapy; 6) >=Grade 3 non-hematological laboratory abnormalities with clinical symptoms that persisted >7 days; 7) Other Grade 3 toxicity lasting >7 days or Grade 4 non-hematological toxicity of any duration; 8) Failure to administer >=75 percent (%) of the planned administration number of study drug in Cycle 1 as a result of treatment-related toxicity. Here, number of participants who had DLT were reported. | Cycle 0 and Cycle 1 (Cycle 0=4 days, Cycle 1=28 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAE was defined as an adverse event (AE) that emerged during time from first dose to 30 days following last dose of drug, having been absent at pretreatment or reemerged during treatment, having been present at pretreatment but stopped before treatment, or worsened in severity during treatment relative to pretreatment state, when AE was continuous. Number of participants with TEAEs were reported based on their safety assessments of laboratory tests, physical examination, regular measurement of vital signs, body weight, echocardiograms/multigated acquisition (MUGA) scans to assess left ventricular ejection fraction, eastern cooperative oncology group-performance status (ECOG-PS) and electrocardiograms parameter values. SAE was defined as untoward medical occurrence that at any dose resulted in death; was life threatening; resulted in persistent or significant disability; was congenital anomaly or medically important due to other reasons than above mentioned criteria. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Eisai Trial Site | Isehara | Kanagawa | Japan | |||
| Eisai Trial Site |
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A total of 7 participants were screened and enrolled to receive study treatment.
Participants took part in the study at 2 investigative sites in Japan from 10 January 2017 to 17 June 2020.
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| ID | Title | Description |
|---|---|---|
| FG000 | Tazemetostat 800 mg | Participants received tazemetostat 800 milligram (mg) tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until disease progression (PD), development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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|
The safety/efficacy analysis set included all participants who received at least 1 administration of the study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Tazemetostat 800 mg | Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Dose-limiting Toxicities (DLTs) | DLTs as per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) were defined as: 1) Grade 4 neutropenia for greater than (>) 7 days; 2) greater than or equal to (>=) Grade 3 febrile neutropenia; 3) Grade 4 thrombocytopenia and Grade 3 thrombocytopenia with bleeding; 4) Grade 4 anemia or anemia requiring erythrocyte transfusion; 5) >=Grade 3 nausea, vomiting, or diarrhea that persisted >7 days despite maximal medical therapy; 6) >=Grade 3 non-hematological laboratory abnormalities with clinical symptoms that persisted >7 days; 7) Other Grade 3 toxicity lasting >7 days or Grade 4 non-hematological toxicity of any duration; 8) Failure to administer >=75 percent (%) of the planned administration number of study drug in Cycle 1 as a result of treatment-related toxicity. Here, number of participants who had DLT were reported. | DLT analysis set included all participants who completed treatment Cycles 0 and 1 without major protocol deviations with at least 75% of treatment compliance in Cycle 1 and were assessed for DLT, and participants who experienced DLT during Cycles 0 and 1. Participants with less than 75% treatment compliance in Cycle 1 due to a reason other than toxicity up to Cycle 1 Day 28 were not included in this analysis set. | Posted | Count of Participants | Participants | Cycle 0 and Cycle 1 (Cycle 0=4 days, Cycle 1=28 days) |
From the date of first dose up to 30 days after the last dose of study drug (up to 40 months)
The safety analysis set included all participants who received at least 1 administration of the study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tazemetostat 800 mg | Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Intestinal perforation | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 22.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Inquiry Service | Eisai Co., Ltd. | eisai-chiken_hotline@hhc.eisai.co.jp |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 18, 2018 | Jan 12, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 18, 2019 | Jan 12, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D012008 | Recurrence |
| D016393 | Lymphoma, B-Cell |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008228 | Lymphoma, Non-Hodgkin |
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| ID | Term |
|---|---|
| C000593333 | tazemetostat |
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| From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) |
| Cmax: Maximum Plasma Concentration of Tazemetostat and Its Metabolite ER-897387 | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) |
| Tmax: Time to Reach Maximum Plasma Concentration (Cmax) of Tazemetostat and Its Metabolite ER-897387 | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) |
| AUC(0-12 Hours): Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post-dose of Tazemetostat and Its Metabolite ER-897387 | Cycle 0 Day 1: 0-12 hours post-dose (Cycle 0 length=4 days) |
| AUC(0-t Hours): Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration of Tazemetostat and Its Metabolite ER-897387 | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) |
| AUC(0-infinity): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of Tazemetostat and Its Metabolite ER-897387 | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) |
| Lambda z: Terminal Phase Elimination Rate Constant of Tazemetostat and Its Metabolite ER-897387 | Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) |
| T1/2: Terminal Half-life of Tazemetostat and Its Metabolite ER-897387 | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
| CL/F: Apparent Total Body Clearance of Tazemetostat | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) |
| Vz/F: Apparent Volume of Distribution at Terminal Phase of Tazemetostat | Vz/F for Cycle 0 Day 1 was calculated as Dose divided by ([lambda z]*[AUC0-infinity]) and for Cycle 1 Day 15 was calculated as Dose divided by ([lambda z]*[AUC0-tau]). | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
| MRT: Mean Residence Time of Tazemetostat and Its Metabolite ER-897387 | MRT of tazemetostat and its metabolite ER-897387 was calculated as MRT=AUMC(0-infinity)/AUC(0-infinity), where AUMC(0-infinity) was the area under the first moment curve extrapolated to infinity and AUC(0-infinity) was area under the concentration-time curve from zero time extrapolated to infinite time. | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) |
| AUC(0-tau): Area Under the Plasma Concentration-time Curve Over the Dosing Interval of Tazemetostat and Its Metabolite ER-897387 | Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
| Css,Av: Average Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387 | Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
| Css,Max: Maximum Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387 | Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
| Css,Min: Minimum Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387 | Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
| PTF: Peak-trough Fluctuation Ratio of Tazemetostat and Its Metabolite ER-897387 | The PTF within complete dosing interval at steady state, calculated as PTF (%) = ([Cmax - Cmin]/Cav) multiplied by 100. Here, Cmin means the minimum plasma concentration, Cmax means the maximum plasma concentration and Cav means the average plasma concentration of drug and metabolite. | Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
| Tss,Max: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State of Tazemetostat and Its Metabolite ER-897387 | Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
| CLss/F: Apparent Total Body Clearance of Tazemetostat at Steady State | Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
| Rac (Cmax): Accumulation Ratio of Cmax for Tazemetostat and Its Metabolite ER-897387 | Rac (Cmax) was calculated as the ratio of maximum observed concentration at steady state (Css,max) on Cycle 1 Day 15 divided by Cmax on Cycle 0 Day 1. | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) and Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
| Rac (AUC): Accumulation Ratio of AUC for Tazemetostat and Its Metabolite ER-897387 | Rac (AUC) was calculated as the ratio of AUC(0-tau) on Cycle 1 Day 15 divided by AUC(0-12 hours) on Cycle 0 Day 1. | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) and Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
| Rss: Steady State Accumulation Ratio of Tazemetostat and Its Metabolite ER-897387 | Rss was calculated as the ratio of AUC(0-tau) on Cycle 1 Day 15 divided by AUC(0-infinity) on Cycle 0 Day 1. | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) and Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
| Ae: Amount of Unchanged Drug Tazemetostat Excreted in Urine | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
| Fe: Fraction of Tazemetostat Dose Excreted in Urine | The fraction of dose excreted in urine was calculated as: Cumulative amount of unchanged drug excreted in urine (Ae)/Dose*100. | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
| CLR: Renal Clearance of Tazemetostat | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
| Percentage of Participants With Objective Response | Objective response was assessed by investigator based on the Lugano Classification (CT-Based) response criteria. Objective response rate was defined as the percentage of participants who had a Best Overall Response (BOR) of complete response (CR) or partial response (PR). CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | From the date of first dose of study drug to the date of first documentation of disease progression or death, whichever occurred first (up to 39 months) |
| Chuo-ku |
| Tokyo |
| Japan |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Secondary | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAE was defined as an adverse event (AE) that emerged during time from first dose to 30 days following last dose of drug, having been absent at pretreatment or reemerged during treatment, having been present at pretreatment but stopped before treatment, or worsened in severity during treatment relative to pretreatment state, when AE was continuous. Number of participants with TEAEs were reported based on their safety assessments of laboratory tests, physical examination, regular measurement of vital signs, body weight, echocardiograms/multigated acquisition (MUGA) scans to assess left ventricular ejection fraction, eastern cooperative oncology group-performance status (ECOG-PS) and electrocardiograms parameter values. SAE was defined as untoward medical occurrence that at any dose resulted in death; was life threatening; resulted in persistent or significant disability; was congenital anomaly or medically important due to other reasons than above mentioned criteria. | The safety analysis set included all participants who received at least 1 administration of the study drug. | Posted | Count of Participants | Participants | From the date of first dose up to 30 days after the last dose of study drug (up to 40 months) |
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| Secondary | Cmax: Maximum Plasma Concentration of Tazemetostat and Its Metabolite ER-897387 | The pharmacokinetic (PK) analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) |
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| Secondary | Tmax: Time to Reach Maximum Plasma Concentration (Cmax) of Tazemetostat and Its Metabolite ER-897387 | The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. | Posted | Median | Full Range | hours | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) |
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| Secondary | AUC(0-12 Hours): Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post-dose of Tazemetostat and Its Metabolite ER-897387 | The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per milliliter (ng*h/mL) | Cycle 0 Day 1: 0-12 hours post-dose (Cycle 0 length=4 days) |
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| Secondary | AUC(0-t Hours): Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration of Tazemetostat and Its Metabolite ER-897387 | The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) |
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| Secondary | AUC(0-infinity): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of Tazemetostat and Its Metabolite ER-897387 | The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) |
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| Secondary | Lambda z: Terminal Phase Elimination Rate Constant of Tazemetostat and Its Metabolite ER-897387 | Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. | The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. | Posted | Geometric Mean | Geometric Coefficient of Variation | per hour | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) |
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| Secondary | T1/2: Terminal Half-life of Tazemetostat and Its Metabolite ER-897387 | The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. | Posted | Median | Full Range | hour | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
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| Secondary | CL/F: Apparent Total Body Clearance of Tazemetostat | The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter per hour (L/h) | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) |
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| Secondary | Vz/F: Apparent Volume of Distribution at Terminal Phase of Tazemetostat | Vz/F for Cycle 0 Day 1 was calculated as Dose divided by ([lambda z]*[AUC0-infinity]) and for Cycle 1 Day 15 was calculated as Dose divided by ([lambda z]*[AUC0-tau]). | The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter (L) | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
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| Secondary | MRT: Mean Residence Time of Tazemetostat and Its Metabolite ER-897387 | MRT of tazemetostat and its metabolite ER-897387 was calculated as MRT=AUMC(0-infinity)/AUC(0-infinity), where AUMC(0-infinity) was the area under the first moment curve extrapolated to infinity and AUC(0-infinity) was area under the concentration-time curve from zero time extrapolated to infinite time. | The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) |
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| Secondary | AUC(0-tau): Area Under the Plasma Concentration-time Curve Over the Dosing Interval of Tazemetostat and Its Metabolite ER-897387 | The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
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| Secondary | Css,Av: Average Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387 | The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
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| Secondary | Css,Max: Maximum Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387 | The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
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| Secondary | Css,Min: Minimum Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387 | The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
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| Secondary | PTF: Peak-trough Fluctuation Ratio of Tazemetostat and Its Metabolite ER-897387 | The PTF within complete dosing interval at steady state, calculated as PTF (%) = ([Cmax - Cmin]/Cav) multiplied by 100. Here, Cmin means the minimum plasma concentration, Cmax means the maximum plasma concentration and Cav means the average plasma concentration of drug and metabolite. | The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. | Posted | Geometric Mean | Geometric Coefficient of Variation | percentage fluctuation | Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
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| Secondary | Tss,Max: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State of Tazemetostat and Its Metabolite ER-897387 | The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. | Posted | Median | Full Range | hours | Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
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| Secondary | CLss/F: Apparent Total Body Clearance of Tazemetostat at Steady State | The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/h | Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
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| Secondary | Rac (Cmax): Accumulation Ratio of Cmax for Tazemetostat and Its Metabolite ER-897387 | Rac (Cmax) was calculated as the ratio of maximum observed concentration at steady state (Css,max) on Cycle 1 Day 15 divided by Cmax on Cycle 0 Day 1. | The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) and Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
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| Secondary | Rac (AUC): Accumulation Ratio of AUC for Tazemetostat and Its Metabolite ER-897387 | Rac (AUC) was calculated as the ratio of AUC(0-tau) on Cycle 1 Day 15 divided by AUC(0-12 hours) on Cycle 0 Day 1. | The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) and Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
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| Secondary | Rss: Steady State Accumulation Ratio of Tazemetostat and Its Metabolite ER-897387 | Rss was calculated as the ratio of AUC(0-tau) on Cycle 1 Day 15 divided by AUC(0-infinity) on Cycle 0 Day 1. | The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) and Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
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| Secondary | Ae: Amount of Unchanged Drug Tazemetostat Excreted in Urine | The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. Here number analyzed "n" signifies participants who were evaluable for this outcome measure at given time points. | Posted | Geometric Mean | Geometric Coefficient of Variation | mg | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
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| Secondary | Fe: Fraction of Tazemetostat Dose Excreted in Urine | The fraction of dose excreted in urine was calculated as: Cumulative amount of unchanged drug excreted in urine (Ae)/Dose*100. | The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. Here number analyzed "n" signifies participants who were evaluable for this outcome measure at given time points. | Posted | Geometric Mean | Geometric Coefficient of Variation | percentage of dose | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
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| Secondary | CLR: Renal Clearance of Tazemetostat | The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. Here number analyzed "n" signifies participants who were evaluable for this outcome measure at given time points. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/h | Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days) |
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| Secondary | Percentage of Participants With Objective Response | Objective response was assessed by investigator based on the Lugano Classification (CT-Based) response criteria. Objective response rate was defined as the percentage of participants who had a Best Overall Response (BOR) of complete response (CR) or partial response (PR). CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | The efficacy analysis set included all participants who received at least 1 administration of the study drug. | Posted | Number | 95% Confidence Interval | percentage of participants | From the date of first dose of study drug to the date of first documentation of disease progression or death, whichever occurred first (up to 39 months) |
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| 0 |
| 7 |
| 2 |
| 7 |
| 7 |
| 7 |
| Squamous cell carcinoma of the tongue | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 22.0 | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA 22.0 | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 22.0 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 22.0 | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 22.0 | Systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA 22.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
|
| Anal fissure | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
|
| Cheilitis | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
|
| Epigastric discomfort | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
|
| Proctalgia | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 22.0 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 22.0 | Systematic Assessment |
|
| Malaise | General disorders | MedDRA 22.0 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 22.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 22.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
|
| Paronychia | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
|
| Muscle strain | Injury, poisoning and procedural complications | MedDRA 22.0 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 22.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 22.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 22.0 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 22.0 | Systematic Assessment |
|
| Blood triglycerides increased | Investigations | MedDRA 22.0 | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA 22.0 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 22.0 | Systematic Assessment |
|
| Hyperphosphatasaemia | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
|
| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
|
| Haemarthrosis | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
|
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
|
| Synovial cyst | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
|
| Tumour associated fever | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 22.0 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 22.0 | Systematic Assessment |
|
| Middle insomnia | Psychiatric disorders | MedDRA 22.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
|
| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
|
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
|
| Skin swelling | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 22.0 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
|
Not provided
Not provided
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
|
| ER-897387 (Cycle 1 Day 15) |
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