| Primary | Part 1: Area Under the Plasma Concentration-Time Curve From Time 0 to 12 Hours of Quantifiable Concentration (AUC0-12h) of Tazemetostat | Blood samples were collected at specified timepoints. AUC0-12h was assessed using non-compartmental data analysis method. AUC0-12h was estimated by a combination of linear trapezoidal method on concentrations going up and logarithmic trapezoidal method on concentrations going down (Linear up/Log down method). | The Pharmacokinetic (PK) population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 1 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or itraconazole. | Posted | | Geometric Mean | Geometric Coefficient of Variation | hours*nanogram/milliliter (h*ng/mL) | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 15 | | | | ID | Title | Description |
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| OG000 | Part 1: Tazemetostat | Participants received a single oral dose of 400 mg tazemetostat on Cycle 1 Day 1, BID dose of tazemetostat 400 mg on Days 3 to 14 and single dose of tazemetostat 400 mg on Day 15. From Days 21 to 35, they received a 400 mg BID dose of tazemetostat. On Cycle 1 Day 36, they received a single dose of 400 mg tazemetostat. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 40 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
| | | Title | Denominators | Categories |
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| Cycle 1 Day 1 | | | | Cycle 1 Day 15 | | |
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| Primary | Part 1: Maximum Observed Plasma Concentration (Cmax) of Tazemetostat | Blood samples were collected at specified timepoints. Cmax was assessed using non-compartmental data analysis method. | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 1 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or itraconazole. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 36, 48, and 72 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 15 | | | | ID | Title | Description |
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| OG000 | Part 1: Tazemetostat | Participants received a single oral dose of 400 mg tazemetostat on Cycle 1 Day 1, BID dose of tazemetostat 400 mg on Days 3 to 14 and single dose of tazemetostat 400 mg on Day 15. From Days 21 to 35, they received a 400 mg BID dose of tazemetostat. On Cycle 1 Day 36, they received a single dose of 400 mg tazemetostat. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 40 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Primary | Part 2: AUC0-12h of Tazemetostat | Blood samples were collected at specified timepoints. AUC0-12h was assessed using non-compartmental data analysis method. AUC0-12h was estimated by a combination of linear trapezoidal method on concentrations going up and logarithmic trapezoidal method on concentrations going down (Linear up/Log down method). | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 2 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or rifampin. | Posted | | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 15 | | | | ID | Title | Description |
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| OG000 | Part 2: Tazemetostat | Participants received a single oral dose of 800 mg tazemetostat on Cycle 1 Day 1, BID dose of 800 mg of tazemetostat from Days 3 to 14 and a single oral dose of 800 mg tazemetostat on Day 15. From Days 17 to 23, they received an 800 mg BID dose of tazemetostat. On Day 24, subjects received a single dose of 800 mg tazemetostat. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 27 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Primary | Part 2: Cmax of Tazemetostat | Blood samples were collected at specified timepoints. Cmax was assessed using non-compartmental data analysis method. | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 2 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or rifampin. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 15 | | | | ID | Title | Description |
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| OG000 | Part 2: Tazemetostat | Participants received a single oral dose of 800 mg tazemetostat on Cycle 1 Day 1, BID dose of 800 mg of tazemetostat from Days 3 to 14 and a single oral dose of 800 mg tazemetostat on Day 15. From Days 17 to 23, they received an 800 mg BID dose of tazemetostat. On Day 24, subjects received a single dose of 800 mg tazemetostat. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 27 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Secondary | Part 1: AUC0-12h of EPZ-6930 After Tazemetostat Alone at Steady-State | Blood samples were collected at specified timepoints. AUC0-12h was assessed using non-compartmental data analysis method. AUC0-12h was estimated by a combination of linear trapezoidal method on concentrations going up and logarithmic trapezoidal method on concentrations going down (Linear up/Log down method). | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 1 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or itraconazole. | Posted | | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours post-dose on Cycle 1 Day 15 | | | | ID | Title | Description |
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| OG000 | Part 1: Tazemetostat | Participants received a single oral dose of 400 mg tazemetostat on Cycle 1 Day 1, BID dose of tazemetostat 400 mg on Days 3 to 14 and single dose of tazemetostat 400 mg on Day 15. From Days 21 to 35, they received a 400 mg BID dose of tazemetostat. On Cycle 1 Day 36, they received a single dose of 400 mg tazemetostat. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 40 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Secondary | Part 1: AUC0-12h of Tazemetostat and EPZ-6930 After Tazemetostat at Steady-State With Itraconazole | Blood samples were collected at specified timepoints. AUC0-12h was assessed using non-compartmental data analysis method. AUC0-12h was estimated by a combination of linear trapezoidal method on concentrations going up and logarithmic trapezoidal method on concentrations going down (Linear up/Log down method). | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 1 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or itraconazole. | Posted | | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours post-dose on Cycle 1 Day 36 | | | | ID | Title | Description |
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| OG000 | Part 1: Tazemetostat + Itraconazole | Participants received a single oral dose of 400 mg tazemetostat on Cycle 1 Day 1, BID dose of tazemetostat 400 mg on Days 3 to 14 and single dose of tazemetostat 400 mg on Day 15. A single oral dose of 200 mg itraconazole was administered daily from Day 18 to Day 20. From Days 21 to 35, they received a 400 mg BID dose of tazemetostat co-administered with a single dose of oral 200 mg itraconazole. Itraconazole was also administered on Days 37 and 38 as a single oral 200 mg daily dose. On Cycle 1 Day 36, they received a single dose of 400 mg tazemetostat co-administered with a single dose of oral 200 mg itraconazole. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 40 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Secondary | Part 1: Cmax of EPZ-6930 After Tazemetostat Alone at Steady-State | Blood samples were collected at specified timepoints. Cmax was assessed using non-compartmental data analysis method. | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 1 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or itraconazole. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 36, and 72 hours post-dose on Cycle 1 Day 15 | | | | ID | Title | Description |
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| OG000 | Part 1: Tazemetostat | Participants received a single oral dose of 400 mg tazemetostat on Cycle 1 Day 1, BID dose of tazemetostat 400 mg on Days 3 to 14 and single dose of tazemetostat 400 mg on Day 15. From Days 21 to 35, they received a 400 mg BID dose of tazemetostat. On Cycle 1 Day 36, they received a single dose of 400 mg tazemetostat. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 40 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Secondary | Part 1: Cmax of Tazemetostat and EPZ-6930 After Tazemetostat at Steady State With Itraconazole | Blood samples were collected at specified timepoints. Cmax was assessed using non-compartmental data analysis method. | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 1 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or itraconazole. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 36, and 72 hours post-dose on Cycle 1 Day 36 | | | | ID | Title | Description |
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| OG000 | Part 1: Tazemetostat + Itraconazole | Participants received a single oral dose of 400 mg tazemetostat on Cycle 1 Day 1, BID dose of tazemetostat 400 mg on Days 3 to 14 and single dose of tazemetostat 400 mg on Day 15. A single oral dose of 200 mg itraconazole was administered daily from Day 18 to Day 20. From Days 21 to 35, they received a 400 mg BID dose of tazemetostat co-administered with a single dose of oral 200 mg itraconazole. Itraconazole was also administered on Days 37 and 38 as a single oral 200 mg daily dose. On Cycle 1 Day 36, they received a single dose of 400 mg tazemetostat co-administered with a single dose of oral 200 mg itraconazole. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 40 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Secondary | Part 1: Observed Time at Cmax (Tmax) of Tazemetostat and EPZ-6930 After Tazemetostat Alone at Steady-State | Blood samples were collected at specified timepoints. Tmax was assessed using non-compartmental data analysis method. | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 1 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or itraconazole. | Posted | | Geometric Mean | Geometric Coefficient of Variation | hour | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 36, and 72 hours post-dose on Cycle 1 Day 15 | | | | ID | Title | Description |
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| OG000 | Part 1: Tazemetostat | Participants received a single oral dose of 400 mg tazemetostat on Cycle 1 Day 1, BID dose of tazemetostat 400 mg on Days 3 to 14 and single dose of tazemetostat 400 mg on Day 15. From Days 21 to 35, they received a 400 mg BID dose of tazemetostat. On Cycle 1 Day 36, they received a single dose of 400 mg tazemetostat. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 40 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Secondary | Part 1: Tmax of Tazemetostat and EPZ-6930 After Tazemetostat at Steady-State With Itraconazole | Blood samples were collected at specified timepoints. Tmax was assessed using non-compartmental data analysis method. | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 1 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or itraconazole. | Posted | | Geometric Mean | Geometric Coefficient of Variation | hour | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 36, and 72 hours post-dose on Cycle 1 Day 36 | | | | ID | Title | Description |
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| OG000 | Part 1: Tazemetostat + Itraconazole | Participants received a single oral dose of 400 mg tazemetostat on Cycle 1 Day 1, BID dose of tazemetostat 400 mg on Days 3 to 14 and single dose of tazemetostat 400 mg on Day 15. A single oral dose of 200 mg itraconazole was administered daily from Day 18 to Day 20. From Days 21 to 35, they received a 400 mg BID dose of tazemetostat co-administered with a single dose of oral 200 mg itraconazole. Itraconazole was also administered on Days 37 and 38 as a single oral 200 mg daily dose. On Cycle 1 Day 36, they received a single dose of 400 mg tazemetostat co-administered with a single dose of oral 200 mg itraconazole. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 40 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Secondary | Part 1: Apparent Terminal Elimination Half-Life (t1/2) of Tazemetostat and EPZ-6930 After Tazemetostat Alone at Steady-State | Blood samples were collected at specified timepoints. T1/2 was assessed using non-compartmental data analysis method. | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 1 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or itraconazole. Only data from the participants analyzed were reported. | Posted | | Median | Full Range | hour | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 36, and 72 hours post-dose on Cycle 1 Day 15 | | | | ID | Title | Description |
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| OG000 | Part 1: Tazemetostat | Participants received a single oral dose of 400 mg tazemetostat on Cycle 1 Day 1, BID dose of tazemetostat 400 mg on Days 3 to 14 and single dose of tazemetostat 400 mg on Day 15. From Days 21 to 35, they received a 400 mg BID dose of tazemetostat. On Cycle 1 Day 36, they received a single dose of 400 mg tazemetostat. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 40 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Secondary | Part 1: T1/2 of Tazemetostat and EPZ-6930 After Tazemetostat at Steady-State With Itraconazole | Blood samples were collected at specified timepoints. T1/2 was assessed using non-compartmental data analysis method. | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 1 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or itraconazole. Only data from the participants analyzed were reported. | Posted | | Median | Full Range | hour | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 36, and 72 hours post-dose on Cycle 1 Day 36 | | | | ID | Title | Description |
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| OG000 | Part 1: Tazemetostat + Itraconazole | Participants received a single oral dose of 400 mg tazemetostat on Cycle 1 Day 1, BID dose of tazemetostat 400 mg on Days 3 to 14 and single dose of tazemetostat 400 mg on Day 15. A single oral dose of 200 mg itraconazole was administered daily from Day 18 to Day 20. From Days 21 to 35, they received a 400 mg BID dose of tazemetostat co-administered with a single dose of oral 200 mg itraconazole. Itraconazole was also administered on Days 37 and 38 as a single oral 200 mg daily dose. On Cycle 1 Day 36, they received a single dose of 400 mg tazemetostat co-administered with a single dose of oral 200 mg itraconazole. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 40 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Secondary | Part 2: AUC0-12h of EPZ-6930 After Tazemetostat Alone at Steady-State | Blood samples were collected at specified timepoints. AUC0-12h was assessed using non-compartmental data analysis method. AUC0-12h was estimated by a combination of linear trapezoidal method on concentrations going up and logarithmic trapezoidal method on concentrations going down (Linear up/Log down method). | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 2 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or rifampin. | Posted | | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours post-dose on Cycle 1 Day 15 | | | | ID | Title | Description |
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| OG000 | Part 2: Tazemetostat | Participants received a single oral dose of 800 mg tazemetostat on Cycle 1 Day 1, BID dose of 800 mg of tazemetostat from Days 3 to 14 and a single oral dose of 800 mg tazemetostat on Day 15. From Days 17 to 23, they received an 800 mg BID dose of tazemetostat. On Day 24, subjects received a single dose of 800 mg tazemetostat. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 27 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Secondary | Part 2: AUC0-12h of Tazemetostat and EPZ-6930 After Tazemetostat at Steady-State With Rifampin | Blood samples were collected at specified timepoints. AUC0-12h was assessed using non-compartmental data analysis method. AUC0-12h was estimated by a combination of linear trapezoidal method on concentrations going up and logarithmic trapezoidal method on concentrations going down (Linear up/Log down method). | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 2 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or rifampin. | Posted | | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Cycle 1 Day 24 | | | | ID | Title | Description |
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| OG000 | Part 2: Tazemetostat + Rifampin | Participants received a single oral dose of 800 mg tazemetostat on Cycle 1 Day 1, BID dose of 800 mg of tazemetostat from Days 3 to 14 and a single oral dose of 800 mg tazemetostat on Day 15. From Days 17 to 23, they received an 800 mg BID dose of tazemetostat co-administered with a single dose of oral 600 mg rifampin. On Day 24, subjects received a single dose of 800 mg tazemetostat co-administered with a single dose of oral 600 mg rifampin. Rifampin was also administered on Cycle 1 Day 25 as a single oral 600 mg dose. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 27 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Secondary | Part 2: Cmax of EPZ-6930 After Tazemetostat Alone at Steady-State | Blood samples were collected at specified timepoints. Cmax was assessed using non-compartmental data analysis method. | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 2 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or rifampin. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours post-dose on Cycle 1 Day 15 | | | | ID | Title | Description |
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| OG000 | Part 2: Tazemetostat | Participants received a single oral dose of 800 mg tazemetostat on Cycle 1 Day 1, BID dose of 800 mg of tazemetostat from Days 3 to 14 and a single oral dose of 800 mg tazemetostat on Day 15. From Days 17 to 23, they received an 800 mg BID dose of tazemetostat. On Day 24, subjects received a single dose of 800 mg tazemetostat. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 27 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Secondary | Part 2: Cmax of Tazemetostat and EPZ-6930 After Tazemetostat at Steady State With Rifampin | Blood samples were collected at specified timepoints. Cmax was assessed using non-compartmental data analysis method. | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 2 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or rifampin. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 hours post-dose on Cycle 1 Day 24 | | | | ID | Title | Description |
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| OG000 | Part 2: Tazemetostat + Rifampin | Participants received a single oral dose of 800 mg tazemetostat on Cycle 1 Day 1, BID dose of 800 mg of tazemetostat from Days 3 to 14 and a single oral dose of 800 mg tazemetostat on Day 15. From Days 17 to 23, they received an 800 mg BID dose of tazemetostat co-administered with a single dose of oral 600 mg rifampin. On Day 24, subjects received a single dose of 800 mg tazemetostat co-administered with a single dose of oral 600 mg rifampin. Rifampin was also administered on Cycle 1 Day 25 as a single oral 600 mg dose. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 27 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Secondary | Part 2: Tmax of Tazemetostat and EPZ-6930 After Tazemetostat Alone at Steady-State | Blood samples were collected at specified timepoints. Tmax was assessed using non-compartmental data analysis method. | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 2 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or rifampin. | Posted | | Geometric Mean | Geometric Coefficient of Variation | hour | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours post-dose on Cycle 1 Day 15 | | | | ID | Title | Description |
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| OG000 | Part 2: Tazemetostat | Participants received a single oral dose of 800 mg tazemetostat on Cycle 1 Day 1, BID dose of 800 mg of tazemetostat from Days 3 to 14 and a single oral dose of 800 mg tazemetostat on Day 15. From Days 17 to 23, they received an 800 mg BID dose of tazemetostat. On Day 24, subjects received a single dose of 800 mg tazemetostat. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 27 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Secondary | Part 2: Tmax of Tazemetostat and EPZ-6930 After Tazemetostat at Steady-State With Rifampin | Blood samples were collected at specified timepoints. Tmax was assessed using non-compartmental data analysis method. | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 2 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or rifampin. | Posted | | Mean | Standard Deviation | hour | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 hours post-dose on Cycle 1 Day 24 | | | | ID | Title | Description |
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| OG000 | Part 2: Tazemetostat + Rifampin | Participants received a single oral dose of 800 mg tazemetostat on Cycle 1 Day 1, BID dose of 800 mg of tazemetostat from Days 3 to 14 and a single oral dose of 800 mg tazemetostat on Day 15. From Days 17 to 23, they received an 800 mg BID dose of tazemetostat co-administered with a single dose of oral 600 mg rifampin. On Day 24, subjects received a single dose of 800 mg tazemetostat co-administered with a single dose of oral 600 mg rifampin. Rifampin was also administered on Cycle 1 Day 25 as a single oral 600 mg dose. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 27 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Secondary | Part 2: T1/2 of Tazemetostat and EPZ-6930 EPZ-6930 After Tazemetostat Alone at Steady-State | Blood samples were collected at specified timepoints. T1/2 was assessed using non-compartmental data analysis method. | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 2 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or rifampin. Only data from the participants analyzed were reported. | Posted | | Median | Full Range | hour | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours post-dose on Cycle 1 Day 15 | | | | ID | Title | Description |
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| OG000 | Part 2: Tazemetostat | Participants received a single oral dose of 800 mg tazemetostat on Cycle 1 Day 1, BID dose of 800 mg of tazemetostat from Days 3 to 14 and a single oral dose of 800 mg tazemetostat on Day 15. From Days 17 to 23, they received an 800 mg BID dose of tazemetostat. On Day 24, subjects received a single dose of 800 mg tazemetostat. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 27 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Secondary | Part 2: T1/2 of Tazemetostat and EPZ-6930 After Tazemetostat at Steady-State With Rifampin | Blood samples were collected at specified timepoints. T1/2 was assessed using non-compartmental data analysis method. | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 2 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or rifampin. Only data from the participants analyzed were reported. | Posted | | Median | Full Range | hour | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 hours post-dose on Cycle 1 Day 24 | | | | ID | Title | Description |
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| OG000 | Part 2: Tazemetostat + Rifampin | Participants received a single oral dose of 800 mg tazemetostat on Cycle 1 Day 1, BID dose of 800 mg of tazemetostat from Days 3 to 14 and a single oral dose of 800 mg tazemetostat on Day 15. From Days 17 to 23, they received an 800 mg BID dose of tazemetostat co-administered with a single dose of oral 600 mg rifampin. On Day 24, subjects received a single dose of 800 mg tazemetostat co-administered with a single dose of oral 600 mg rifampin. Rifampin was also administered on Cycle 1 Day 25 as a single oral 600 mg dose. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 27 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Other Pre-specified | Part 1: Least Squares Geometric Mean Ratio of Observed Accumulation Ratio of AUC0-12h for Tazemetostat | Blood samples were collected at specified timepoints. AUC0-12h accumulation ratio was assessed using non-compartmental data analysis method. AUC0-12h accumulation ratio was calculated as the ratio of AUC0-12h at steady state (Cycle 1 Day 15) divided by AUC0-12 during the initial dosing interval (Cycle 1 Day 1). | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 1 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or itraconazole. | Posted | | Geometric Least Squares Mean | 90% Confidence Interval | ratio | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 15 | | | | ID | Title | Description |
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| OG000 | Part 1: Tazemetostat | Participants received a single oral dose of 400 mg tazemetostat on Cycle 1 Day 1, BID dose of tazemetostat 400 mg on Days 3 to 14 and single dose of tazemetostat 400 mg on Day 15. From Days 21 to 35, they received a 400 mg BID dose of tazemetostat. On Cycle 1 Day 36, they received a single dose of 400 mg tazemetostat. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 40 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Other Pre-specified | Part 1: Least Squares Geometric Mean Ratio of Cmax Accumulation Ratio for Tazemetostat | Blood samples were collected at specified timepoints. Cmax accumulation ratio was assessed using non-compartmental data analysis method. Cmax accumulation ratio was calculated as the ratio of Cmax at steady state (Cycle 1 Day 15) divided by Cmax during the initial dosing interval (Cycle 1 Day 1). | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 1 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or itraconazole. | Posted | | Geometric Least Squares Mean | 90% Confidence Interval | ratio | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8,12, 36, 48 post-dose on Cycle 1 Day 1, and 72 hours post-dose on Cycle 1 Day 15 | | | | ID | Title | Description |
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| OG000 | Part 1: Tazemetostat | Participants received a single oral dose of 400 mg tazemetostat on Cycle 1 Day 1, BID dose of tazemetostat 400 mg on Days 3 to 14 and single dose of tazemetostat 400 mg on Day 15. From Days 21 to 35, they received a 400 mg BID dose of tazemetostat. On Cycle 1 Day 36, they received a single dose of 400 mg tazemetostat. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 40 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Other Pre-specified | Part 1: Least Squares Geometric Mean Ratio of AUC0-12h After Single Dose of Tazemetostat With Itraconazole | Blood samples were collected at specified timepoints. Drug-drug interaction was assessed using analysis of variance (ANOVA). | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 1 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or itraconazole. | Posted | | Geometric Least Squares Mean | 90% Confidence Interval | ratio | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours post-dose on Cycle 1 Day 1 (without itraconazole) and Cycle 1 Day 21 (with itraconazole) | | | | ID | Title | Description |
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| OG000 | Part 1: Tazemetostat + Itraconazole | Participants received a single oral dose of 400 mg tazemetostat on Cycle 1 Day 1, BID dose of tazemetostat 400 mg on Days 3 to 14 and single dose of tazemetostat 400 mg on Day 15. A single oral dose of 200 mg itraconazole was administered daily from Day 18 to Day 20. From Days 21 to 35, they received a 400 mg BID dose of tazemetostat co-administered with a single dose of oral 200 mg itraconazole. Itraconazole was also administered on Days 37 and 38 as a single oral 200 mg daily dose. On Cycle 1 Day 36, they received a single dose of 400 mg tazemetostat co-administered with a single dose of oral 200 mg itraconazole. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 40 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Other Pre-specified | Part 1: Least Squares Geometric Mean Ratio of Cmax After Single Dose of Tazemetostat With Itraconazole | Blood samples were collected at specified timepoints. Drug-drug interaction was assessed using ANOVA. | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 1 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or itraconazole. | Posted | | Geometric Least Squares Mean | 90% Confidence Interval | ratio | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours post-dose on Cycle 1 Day 1 (without itraconazole) and Cycle 1 Day 21 (with itraconazole) | | | | ID | Title | Description |
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| OG000 | Part 1: Tazemetostat + Itraconazole | Participants received a single oral dose of 400 mg tazemetostat on Cycle 1 Day 1, BID dose of tazemetostat 400 mg on Days 3 to 14 and single dose of tazemetostat 400 mg on Day 15. A single oral dose of 200 mg itraconazole was administered daily from Day 18 to Day 20. From Days 21 to 35, they received a 400 mg BID dose of tazemetostat co-administered with a single dose of oral 200 mg itraconazole. Itraconazole was also administered on Days 37 and 38 as a single oral 200 mg daily dose. On Cycle 1 Day 36, they received a single dose of 400 mg tazemetostat co-administered with a single dose of oral 200 mg itraconazole. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 40 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Other Pre-specified | Part 1: Least Squares Geometric Mean Ratio of AUC0-12h After Tazemetostat at Steady-State With Itraconazole | Blood samples were collected at specified timepoints. Drug-drug interaction was assessed using ANOVA. | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 1 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or itraconazole. | Posted | | Geometric Least Squares Mean | 90% Confidence Interval | ratio | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours post-dose on Cycle 1 Day 15 (without itraconazole) and Cycle 1 Day 36 (with itraconazole) | | | | ID | Title | Description |
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| OG000 | Part 1: Tazemetostat + Itraconazole | Participants received a single oral dose of 400 mg tazemetostat on Cycle 1 Day 1, BID dose of tazemetostat 400 mg on Days 3 to 14 and single dose of tazemetostat 400 mg on Day 15. A single oral dose of 200 mg itraconazole was administered daily from Day 18 to Day 20. From Days 21 to 35, they received a 400 mg BID dose of tazemetostat co-administered with a single dose of oral 200 mg itraconazole. Itraconazole was also administered on Days 37 and 38 as a single oral 200 mg daily dose. On Cycle 1 Day 36, they received a single dose of 400 mg tazemetostat co-administered with a single dose of oral 200 mg itraconazole. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 40 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Other Pre-specified | Part 1: Least Squares Geometric Mean Ratio of Cmax After Tazemetostat at Steady-State With Itraconazole | Blood samples were collected at specified timepoints. Drug-drug interaction was assessed using ANOVA. | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 1 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or itraconazole. | Posted | | Geometric Least Squares Mean | 90% Confidence Interval | ratio | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 36, and 72 hours post-dose on Cycle 1 Day 15 (without itraconazole) and Cycle 1 Day 36 (with itraconazole) | | | | ID | Title | Description |
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| OG000 | Part 1: Tazemetostat + Itraconazole | Participants received a single oral dose of 400 mg tazemetostat on Cycle 1 Day 1, BID dose of tazemetostat 400 mg on Days 3 to 14 and single dose of tazemetostat 400 mg on Day 15. A single oral dose of 200 mg itraconazole was administered daily from Day 18 to Day 20. From Days 21 to 35, they received a 400 mg BID dose of tazemetostat co-administered with a single dose of oral 200 mg itraconazole. Itraconazole was also administered on Days 37 and 38 as a single oral 200 mg daily dose. On Cycle 1 Day 36, they received a single dose of 400 mg tazemetostat co-administered with a single dose of oral 200 mg itraconazole. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 40 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Other Pre-specified | Part 2: Least Squares Geometric Mean Ratio of Observed Accumulation Ratio of AUC0-12h for Tazemetostat | Blood samples were collected at specified timepoints. AUC0-12h accumulation ratio was assessed using non-compartmental data analysis method. AUC0-12h accumulation ratio was calculated as the ratio of AUC0-12h at steady state (Cycle 1 Day 15) divided by AUC0-12h during the initial dosing interval (Cycle 1 Day 1). | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 2 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or rifampin. | Posted | | Geometric Least Squares Mean | 90% Confidence Interval | ratio | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8,12, 24, 36, and 48 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 15 | | | | ID | Title | Description |
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| OG000 | Part 2: Tazemetostat | Participants received a single oral dose of 800 mg tazemetostat on Cycle 1 Day 1, BID dose of 800 mg of tazemetostat from Days 3 to 14 and a single oral dose of 800 mg tazemetostat on Day 15. From Days 17 to 23, they received an 800 mg BID dose of tazemetostat. On Day 24, subjects received a single dose of 800 mg tazemetostat. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 27 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Other Pre-specified | Part 2: Least Squares Geometric Mean Ratio of Cmax Accumulation Ratio for Tazemetostat | Blood samples were collected at specified timepoints. Cmax accumulation ratio was assessed using non-compartmental data analysis method. Cmax accumulation ratio was calculated as the ratio of Cmax at steady state (Cycle 1 Day 15) divided by Cmax during the initial dosing interval (Cycle 1 Day 1). | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 2 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or rifampin. | Posted | | Geometric Least Squares Mean | 90% Confidence Interval | ratio | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8,12, 24, 36, and 48 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 15 | | | | ID | Title | Description |
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| OG000 | Part 2: Tazemetostat | Participants received a single oral dose of 800 mg tazemetostat on Cycle 1 Day 1, BID dose of 800 mg of tazemetostat from Days 3 to 14 and a single oral dose of 800 mg tazemetostat on Day 15. From Days 17 to 23, they received an 800 mg BID dose of tazemetostat. On Day 24, subjects received a single dose of 800 mg tazemetostat. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 27 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Other Pre-specified | Part 2: Least Squares Geometric Mean Ratio of AUC0-12h After Tazemetostat at Steady State With Rifampin | Blood samples were collected at specified timepoints. Drug-drug interaction was assessed using ANOVA. | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 2 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or rifampin. | Posted | | Geometric Least Squares Mean | 90% Confidence Interval | ratio | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Cycle 1 Day 15 (without rifampin) and Cycle 1 Day 24 (with rifampin) | | | | ID | Title | Description |
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| OG000 | Part 2: Tazemetostat + Rifampin | Participants received a single oral dose of 800 mg tazemetostat on Cycle 1 Day 1, BID dose of 800 mg of tazemetostat from Days 3 to 14 and a single oral dose of 800 mg tazemetostat on Day 15. From Days 17 to 23, they received an 800 mg BID dose of tazemetostat co-administered with a single dose of oral 600 mg rifampin. On Day 24, subjects received a single dose of 800 mg tazemetostat co-administered with a single dose of oral 600 mg rifampin. Rifampin was also administered on Cycle 1 Day 25 as a single oral 600 mg dose. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 27 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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| Other Pre-specified | Part 2: Least Squares Geometric Mean Ratio of Cmax After Tazemetostat at Steady State With Rifampin | Blood samples were collected at specified timepoints. Drug-drug interaction was assessed using ANOVA. | The PK population included all participants who had sufficient PK concentration data to calculate steady-state PK parameters in Part 2 and did not have any major protocol deviation that was deemed to greatly alter the steady-state exposure to tazemetostat or rifampin. | Posted | | Geometric Least Squares Mean | 90% Confidence Interval | ratio | | Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours post-dose on Cycle 1 Day 15 (without rifampin) and Cycle 1 Day 24 (with rifampin) | | | | ID | Title | Description |
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| OG000 | Part 2: Tazemetostat + Rifampin | Participants received a single oral dose of 800 mg tazemetostat on Cycle 1 Day 1, BID dose of 800 mg of tazemetostat from Days 3 to 14 and a single oral dose of 800 mg tazemetostat on Day 15. From Days 17 to 23, they received an 800 mg BID dose of tazemetostat co-administered with a single dose of oral 600 mg rifampin. On Day 24, subjects received a single dose of 800 mg tazemetostat co-administered with a single dose of oral 600 mg rifampin. Rifampin was also administered on Cycle 1 Day 25 as a single oral 600 mg dose. Participants continued to receive tazemetostat treatment at the recommended therapeutic dose (oral 800 mg tazemetostat BID), from Day 27 (Cycle 2 Day 1) for each subsequent cycle of 28-day duration until Investigator assessed clinical progression per standard practice, unacceptable treatment related toxicity/withdrawal; survival follow-up (until death/study closure). |
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