Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Mantle-Cell

Lymphoma, B-Cell, Marginal Zone

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Mantle Cell Lymphoma

B-cell Lymphoma

Marginal Zone Lymphoma

Diffuse Large B-Cell Lymphoma

Gastrointestinal Agents

All Drugs and Chemicals

Hypoglycemic Agents

Anti-Infective Agents

Omeprazole

Repaglinide

Fluconazole

Cytochrome P-450 CYP3A Inhibitors

Antacids

Anti-Ulcer Agents

Proton Pump Inhibitors

Enzyme Inhibitors

Clotrimazole

Miconazole

Antifungal Agents

Cytochrome P-450 Enzyme Inhibitors

Hormones

Hormone Antagonists

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.

Tazemetostat is a selective oral small molecule inhibitor of EZH2

Tazemetostat

200mg will be orally administered QD for 4 days in order to determine CYP3A4 inhibition when administered concomitantly with tazemetostat

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.

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.

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.

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

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

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.

Epizyme, Inc.

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 A

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.

Part B

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.

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.

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Advanced Solid tumors

Stage at diagnosis: I

Stage at diagnosis: II

Stage at diagnosis: III

Stage at diagnosis: IV

Stage at diagnosis: Unknown

Progressive disease prior to study entry

Baseline Disease Characteristics and Prior Therapies

Kemly Calixte

Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ-6438

Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ-6438

Part A: Effect of CYP3A Inhibition by Fluconazole on the PK of Tazemetostat (AUC0-t, AUC0-8)

Part A: Cmax of Tazemetostat During Co-administration With Fluconazole

Part: B; Day 1; Treatment: Repaglinide Alone; Analyte: Repaglinide - AUC(0-t)

Part: B; Day 16; Treatment: Repaglinide with Tazemetostat; Analyte: Repaglinide - AUC(0-t)

Part: B; Day 1; Treatment: Repaglinide Alone; Analyte: Repaglinide - AUC(0-∞)

Part: B; Day 16; Treatment: Repaglinide with Tazemetostat; Analyte: Repaglinide - AUC(0-∞)

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.

Part B: The Potential of Tazemetostat to Inhibit or Induce CYP2C8 Using Repaglinide as a Probe Substrate (AUC0-t, AUC0-∞)

Part: B; Day 1; Treatment: Repaglinide Alone; Analyte: Repaglinide

Part: B; Day 16; Treatment: Repaglinide with Tazemetostat; Analyte: Repaglinide

Part B: Cmax of Repaglinide During Co-administration With Tazemetostat

Part: B; Day 1; Treatment: Omeprazole Alone; Analyte: Omeprazole - AUC(0-t)

Part: B; Day 16; Treatment: Omeprazole with Tazemetostat; Analyte: Omeprazole - AUC(0-t)

Part: B; Day 1; Treatment: Omeprazole Alone; Analyte: Omeprazole - AUC(0-∞)

Part: B; Day 16; Treatment: Omeprazole with Tazemetostat; Analyte: Omeprazole - AUC(0-∞)

Part B: The Potential of Tazemetostat to Inhibit or Induce CYP2C19 Using Omeprazole as Probe a Substrate (AUC0-t, AUC0-∞)

Part: B; Day 1; Treatment: Omeprazole Alone; Analyte: Omeprazole

Part: B; Day 16; Treatment: Omeprazole with Tazemetostat; Analyte: Omeprazole

Part B: Cmax of Omeprazole During Co-administration With Tazemetostat

Part: B; Day 16; Treatment: Omeprazole with Tazemetostat; Analyte: EPZ-6438 - AUC(0-t)

Part: B; Day 19; Treatment: Tazemetostat Alone; Analyte: EPZ-6438 - AUC(0-t)

Part B: Effect of Increased Gastric pH by Omeprazole on the PK of Tazemetostat (AUC0-t, AUC0-8)

Part: B; Day 16; Treatment: Omeprazole with Tazemetostat; Analyte: EPZ-6438

Part: B; Day 19; Treatment: Tazemetostat Alone; Analyte: EPZ-6438

Part B: Cmax of Tazemetostat During Co-administration With Omeprazole

Any TEAE

Any TEAE Grade 3 or 4

Any Treatment-Related TEAE

Any Treatment-Related TEAE Grade 3 or 4

Any TEAE Leading to Dose Reduction

Any TEAE Leading to Study Drug Interruption

Any TEAE Leading to Study Drug Discontinuation

Any TESAE

Any Treatment-Related TESAE

Any Protocol Defined AE of Special Interest

Incidence of Treatment-emergent Adverse Events as a Measure of Safety

Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ-6930 (ER-897387)

Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ-6930 (ER-897387)

Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ006931

Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ006931

Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ034163

Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ034163

Part A: PK of Tazemetostat and Its Metabolites After Administration Alone and With Fluconazole (AUC0-t, AUC0-8)

Part A: Tmax of Tazemetostat After Administration Alone and With Fluconazole

Part A: t1/2 of Tazemetostat After Administration Alone and With Fluconazole

Part A: Cmax of Tazemetostat Metabolites After Administration Alone and With Fluconazole

Part A: Tmax of Tazemetostat Metabolites After Administration Alone and With Fluconazole

Part A: t1/2 of Tazemetostat Metabolites After Administration Alone and With Fluconazole

Part A: Exposure of Fluconazole After Administration of 400 mg Once Daily for 4 Days (AUC0-8)

Part A: Cmax of Fluconazole After Administration of 400mg Once Daily for 4 Days

Part A: Tmax of Fluconazole After Administration of 400mg Once Daily for 4 Days

Complete response (CR)

Partial response (PR)

Stable disease (SD)

Progressive disease (PD)

Not evaluable, missing, or unknown

Objective Response Rate (ORR)

Disease control rate (DCR) at 24 weeks

Number of responders (achieving a CR or PR)

Advanced Solid Tumors

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 .

Overall Study

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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