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

• Sponsor: Epizyme, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03028103
• Collaborator: (none)
• Enrollment: 32
• Locations: 3
• Arm: 1
• Actual Duration (Months): 32.1
• Patients Per Site: 10.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B Cell Lymphoma; Primary Mediastinal Lymphoma; Mantle Cell Lymphoma; Advanced Solid Tumor; Marginal Zone Lymphoma	Drug: Tazemetostat; Drug: Fluconazole; Drug: Omeprazole; Drug: Repaglinide	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Multicenter, Two-Part, Phase 1 Study to Characterize the Effects of a Moderate CYP3A Inhibitor on the Pharmacokinetics of Tazemetostat (EPZ-6438) (Part A), the Effects of Tazemetostat on the Pharmacokinetics of CYP2C8 and CYP2C19 Substrates, and the Effect of Increased Gastric pH on the Pharmacokinetics of Tazemetostat (Part B) in Subjects With B-cell Lymphoma or Advanced Solid Tumors
• Actual Study Start Date: Mar 27, 2017
• Actual Primary Completion Date: Oct 31, 2019
• Actual Study Completion Date: Nov 29, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Part A and B 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.

Drug: Tazemetostat; Tazemetostat is a selective oral small molecule inhibitor of EZH2; Other Names: EPZ-6438, E7438 ; Drug: Fluconazole; 200mg will be orally administered QD for 4 days in order to determine CYP3A4 inhibition when administered concomitantly with tazemetostat; Drug: Omeprazole; 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.; Drug: Repaglinide; 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.

Outcome Measures

Primary Outcome Measures

1. Part A: Effect of CYP3A Inhibition by Fluconazole on the PK of Tazemetostat (AUC0-t, AUC0-8) [Days 15 and 19, 0 to 8 hours post-dose]

2. Part A: Cmax of Tazemetostat During Co-administration With Fluconazole [Days 15 and 19, 0 to 8 hours post-dose]

3. Part B: The Potential of Tazemetostat to Inhibit or Induce CYP2C8 Using Repaglinide as a Probe Substrate (AUC0-t, AUC0-∞) [Days 1 and 16, 0 to 8 hours post-dose]

4. Part B: Cmax of Repaglinide During Co-administration With Tazemetostat [Days 1 and 16, 0 to 8 hours post-dose]

5. Part B: The Potential of Tazemetostat to Inhibit or Induce CYP2C19 Using Omeprazole as Probe a Substrate (AUC0-t, AUC0-∞) [Days 1 and 16, 0 to 8 hours post-dose]

6. Part B: Cmax of Omeprazole During Co-administration With Tazemetostat [Days 1 and 16, 0 to 8 hours post-dose]

7. Part B: Effect of Increased Gastric pH by Omeprazole on the PK of Tazemetostat (AUC0-t, AUC0-8) [Days 16 and 19, 0 to 8 hours post-dose]

8. Part B: Cmax of Tazemetostat During Co-administration With Omeprazole [Days 16 and 19, 0 to 8 hours post-dose]

Secondary Outcome Measures

1. Incidence of Treatment-emergent Adverse Events as a Measure of Safety [From the first dose of study treatment until the earlier of either 30 days after the discontinuation of study treatment or until the initiation of subsequent anticancer therapy, up to 2 years.]

2. Part A: PK of Tazemetostat and Its Metabolites After Administration Alone and With Fluconazole (AUC0-t, AUC0-8) [Days 15 and 19, 0 to 8 hours post-dose]

3. Part A: Tmax of Tazemetostat After Administration Alone and With Fluconazole [Days 15 and 19, 0 to 8 hours post-dose]

4. Part A: t1/2 of Tazemetostat After Administration Alone and With Fluconazole [Days 15 and 19, 0 to 8 hours post-dose]

5. Part A: Cmax of Tazemetostat Metabolites After Administration Alone and With Fluconazole [Days 15 and 19, 0 to 8 hours post-dose]

6. Part A: Tmax of Tazemetostat Metabolites After Administration Alone and With Fluconazole [Days 15 and 19, 0 to 8 hours post-dose]

7. Part A: t1/2 of Tazemetostat Metabolites After Administration Alone and With Fluconazole [Days 15 and 19, 0 to 8 hours post-dose]

8. Part A: Exposure of Fluconazole After Administration of 400 mg Once Daily for 4 Days (AUC0-8) [Day 19, 0 to 8 hours post-dose]

9. Part A: Cmax of Fluconazole After Administration of 400mg Once Daily for 4 Days [Day 19, 0 to 8 hours post-dose]

10. Part A: Tmax of Fluconazole After Administration of 400mg Once Daily for 4 Days [Day 19, 0 to 8 hours post-dose]

11. 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 . [Within 28 days of Day 1, 8 weeks, 16 weeks, 24 weeks]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria

1. Male or female ≥ 18 years of age at time of consent

2. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

3. Has the ability to understand informed consent and provided signed written informed consent

Must meet one of the following criteria:

1. Has histologically confirmed diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL) and have relapsed or refractory disease following at least two lines of prior standard therapy, including alkylator/anthracycline (unless anthracycline-based chemotherapy is contraindicated)/anti-CD20-based therapy (R-CHOP; rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisolone or prednisone, or equivalent) AND must be considered unable to benefit from intensification treatment with autologous hematopoietic stem cell transplantation (ASCT), as defined by meeting at least one of the following criteria:

2. Relapsed following, or refractory to, previous ASCT

3. Did not achieve at least a partial response (PR) to a standard salvage regimen (e.g., R-ICE; rituximab, ifosfamide, carboplatin, etoposide, or R-DHAP; rituximab, dexamethasone, cytarabine, cisplatin)

4. Ineligible for intensification treatment due to age or significant comorbidity

5. Ineligible for intensification treatment due to failure to mobilize an acceptable number of hematopoietic stem cells

6. Refused intensification treatment and/or ASCT Note: Subjects with prior radiotherapy will be included; however, radiotherapy alone will not be considered a separate systemic treatment regimen.

Note: Subjects with prior radiotherapy will be included; however, radiotherapy alone will not be considered a separate systemic treatment regimen.

OR

1. Has histologically confirmed FL, all grades. Subjects must have relapsed/refractory disease following at least 2 standard lines of systemic therapy, including at least 1 anti-CD20-based regimen (eg, rituximab), as well as alkalating agents (eg, cyclophosphamide or bendamustine), and have no curative option with other available therapies OR have a contra-indication to their use. Subjects with prior ASCT may be included. Transformed disease is permitted.

Note: Subjects with prior radiotherapy will be included; however, radiotherapy alone will not be considered a separate systemic treatment regimen.

OR

1. Histologically and/or cytologically confirmed advanced or metastatic solid tumor that has progressed after treatment with approved therapies or for which there are no standard therapies available

2. Must have evaluable or measurable disease

3. Has all prior treatment (i.e., chemotherapy, immunotherapy, radiotherapy) related clinically significant toxicities resolve to ≤ Grade 1 per NCI CTCAE, Version 4.03 or are clinically stable and not clinically significant, at time of consent

4. Time required between the last dose of the latest therapy and the first dose of study drug:

5. Chemotherapy: cytotoxic At least 21 days

6. Chemotherapy: nitrosoureas At least 6 weeks

7. Chemotherapy: non-cytotoxic (e.g., small molecule inhibitor) At least 14 days

8. Monoclonal antibody (ies) At least 28 days

9. Non-antibody immunotherapy (e.g., tumor vaccine) At least 42 days

10. At least 14 days for stereotactic radiosurgery

11. At least 12 weeks for craniospinal, ≥50% radiation of pelvis, or total body irradiation prior to first dose of study drug

12. Autologous hematopoietic cell infusion after high dose therapy At least 60 days

13. Hematopoietic growth factor At least 14 days

14. Has adequate hematologic (bone marrow [BM] and coagulation factors), renal and hepatic function

15. Hemoglobin ≥9 g/dL

16. Platelets ≥75,000/mm3 (≥75 × 10^9/L)

17. ANC: for patients with lymphoma ≥750/mm3 (≥0.75 × 10^{9/L), for patients with advanced solid tumors ≥1,000/mm3 (≥1.0 × 10}9/L),

18. PT <1.5 ULN

19. PTT <1.5 ULN

20. eGFR ≥ 50 mL/min/1.73 m2

21. Conjugated bilirubin <1.5 × ULN

22. AST <3 × ULN

23. ALT <3 × ULN

NOTE: Laboratory results obtained during screening should be used to determine eligibility criteria. In situations where laboratory results are outside the permitted range, the investigator may retest the subject and the subsequent within range screening result may be used to determine the subject's eligibility.

1. Has a QT interval corrected by Fridericia's formula (QTcF) ≤480 msec

2. Subjects with a history of Hepatitis B or C are eligible on the condition that subjects have adequate liver function as defined by the protocol and are hepatitis B surface antigen negative and/or have undetectable HCV RNA.

3. Male subjects must refrain from donating sperm starting at the planned first dose of investigational product (IP) until 30 days following the last dose of IP

4. Male subjects with a female partner of childbearing potential must:

5. Be vasectomized, or

6. Remain abstinent or use a condom as defined in Section 8.3.8.4.2, starting at the planned first dose of IP until 30 days following the last dose of IP. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception.

7. Female partners of male subjects who are of childbearing potential must also adhere to one of the following:

8. Placement of an intrauterine device or intrauterine system.

9. Established use of oral, injected, or implanted hormonal methods of contraception or use of a barrier method of contraception.

10. Progesterone only oral contraception, where inhibition of ovulation is not the primary mode of action.

11. Women of childbearing potential or female partners of male subjects must abide by the contraception measures defined by the protocol

Exclusion criteria:

1. Is pregnant or nursing

2. Has active central nervous system (CNS) or leptomeningeal metastasis

3. Has had a prior malignancy other than the malignancies under study Exception: Subject who has been disease-free for 3 years, or a subject with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.

4. Has thrombocytopenia, neutropenia, or anemia of Grade ≥3 (per CTCAE 4.03 criteria) and any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS).

NOTE: Bone marrow aspirate/biopsy will be conducted following abnormal peripheral blood smear morphology assessment conducted by the local laboratory. Cytogenetic testing and DNA sequencing will be conducted following an abnormal result of bone marrow aspirate/biopsy.

1. Has a prior history of T-LBL/T-ALL.

2. Has had major surgery within 3 weeks prior to enrollment NOTE: Minor surgery (e.g., minor biopsy, central venous catheter placement) is permitted within 3 weeks prior to enrollment.

3. Is unwilling to exclude grapefruit juice, Seville oranges, and grapefruit from the diet and all foods that contain those fruits from time of enrollment to while on study

4. Has cardiovascular impairment, history of congestive heart failure greater than NYHA Class II uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months prior to the planned first dose of tazemetostat; or ventricular cardiac arrhythmia requiring medical treatment

5. Subjects taking medications that are known potent or moderate inducers/ inhibitors of CYP3A4 (including St. John's Wort)

6. Has an active infection or recent history (<30 days before study drug administration) requiring systemic treatment

7. Is immunocompromised, including subjects with known human immunodeficiency virus (HIV) infection

8. Has known hypersensitivity to any of the components of IP.

9. Is unable to take oral medications, has a history of surgery that would interfere with the administration or absorption of oral medication, has malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g., nausea, diarrhea or vomiting) that might impair the bioavailability of IP

10. Has an uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, or psychiatric illness/social situations that would limit compliance with study requirements.

11. Is unwilling to adhere to contraception criteria from time of enrollment in study to at least 30 days after last dose of IP.

12. A history of bleeding (i.e., hemoptysis, hematuria, gastrointestinal blood loss, epistaxis, or others with greater than Grade 1 according to NCI CTCAE Version 4.03) within 1 month prior to beginning therapy or any clinical indications of current active bleeding.

13. Clinical history, current alcohol (ethanol), or illicit drug use which, in the judgment of the investigator, will interfere with the subject's ability to comply with the dosing schedule and protocol-specified evaluations.

14. Regular alcohol consumption averaging more than seven drinks/week for women and 14 drinks/week for men within 6 months of screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arizona Cancer Center	Tucson	Arizona	United States	85719
2	Moffitt Cancer Center	Tampa	Florida	United States	33612
3	Columbia University Medical Center	New York	New York	United States	10032

Sponsors and Collaborators

• Epizyme, Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 28, 2018

More Information

Publications

None provided.

• Responsible Party: Epizyme, Inc.
• ClinicalTrials.gov Identifier: NCT03028103
• Other Study ID Numbers: EZH-105
• First Posted: Jan 23, 2017
• Last Update Posted: Apr 19, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Repaglinide; Fluconazole; Omeprazole

Study Results

Participant Flow

Arm/Group Title	Part A	Part B
Arm/Group Description	Subjects enrolled in Part A received treatment with oral tazemetostat tablets 400 mg twice daily for 24 days beginning on Day 1. Blood samples for the analysis of plasma tazemetostat and its metabolites concentrations were collected predose and over 8 hours after the morning dose of tazemetostat on Day 15. Subjects received fluconazole 400 mg once daily for 4 days starting on Day 16. On Day 19, blood samples for the analysis of plasma tazemetostat, its metabolites, and fluconazole were collected predose and over 8 hours after the morning tazemetostat dose. Tazemetostat 400 mg twice daily continued through Day 24. Subjects then received tazemetostat 800 mg twice daily starting on Day 25.	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.
Period Title: Overall Study
STARTED	16	16
COMPLETED	16	16
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Part A	Part B	Total
Arm/Group Description	Subjects enrolled in Part A received treatment with oral tazemetostat tablets 400 mg twice daily for 24 days beginning on Day 1. Blood samples for the analysis of plasma tazemetostat and its metabolites concentrations were collected predose and over 8 hours after the morning dose of tazemetostat on Day 15. Subjects received fluconazole 400 mg once daily for 4 days starting on Day 16. On Day 19, blood samples for the analysis of plasma tazemetostat, its metabolites, and fluconazole were collected predose and over 8 hours after the morning tazemetostat dose. Tazemetostat 400 mg twice daily continued through Day 24. Subjects then received tazemetostat 800 mg twice daily starting on Day 25.	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 of all reporting groups
Overall Participants	16	16	32
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	9 56.3%	11 68.8%	20 62.5%
>=65 years	7 43.8%	5 31.3%	12 37.5%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	62.9 (15.10)	48.8 (17.75)	55.8 (17.73)
Sex: Female, Male (Count of Participants)
Female	10 62.5%	7 43.8%	17 53.1%
Male	6 37.5%	9 56.3%	15 46.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 6.3%	2 12.5%	3 9.4%
Not Hispanic or Latino	15 93.8%	13 81.3%	28 87.5%
Unknown or Not Reported	0 0%	1 6.3%	1 3.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 12.5%	4 25%	6 18.8%
White	14 87.5%	12 75%	26 81.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	16 100%	16 100%	32 100%
Baseline Disease Characteristics and Prior Therapies (Count of Participants)
Lymphoma	10 62.5%	3 18.8%	13 40.6%
Advanced Solid tumors	6 37.5%	13 81.3%	19 59.4%
Stage at diagnosis: I	0 0%	0 0%	0 0%
Stage at diagnosis: II	1 6.3%	1 6.3%	2 6.3%
Stage at diagnosis: III	5 31.3%	3 18.8%	8 25%
Stage at diagnosis: IV	8 50%	10 62.5%	18 56.3%
Stage at diagnosis: Unknown	2 12.5%	2 12.5%	4 12.5%
Progressive disease prior to study entry	16 100%	16 100%	32 100%

Outcome Measures

1. Primary Outcome

Title	Part A: Effect of CYP3A Inhibition by Fluconazole on the PK of Tazemetostat (AUC0-t, AUC0-8)
Time Frame	Days 15 and 19, 0 to 8 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Part A
Arm/Group Description	Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25.
Measure Participants	14
Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ-6438	1340 (1180)
Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ-6438	4100 (2680)

2. Primary Outcome

Title	Part A: Cmax of Tazemetostat During Co-administration With Fluconazole
Time Frame	Days 15 and 19, 0 to 8 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Part A
Arm/Group Description	Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25.
Measure Participants	14
Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ-6438	426 (337)
Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ-6438	968 (801)

3. Primary Outcome

Title	Part B: The Potential of Tazemetostat to Inhibit or Induce CYP2C8 Using Repaglinide as a Probe Substrate (AUC0-t, AUC0-∞)
Time Frame	Days 1 and 16, 0 to 8 hours post-dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part B
Arm/Group Description	Part B: Subjects enrolled in Part B will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg on Day 1. Administration of tazemetostat 800 mg BID will begin on Day 2. On Day 16, subjects again will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg approximately 1 hour after the morning dose of tazemetostat. Subjects also will receive omeprazole 20 mg once daily in the morning on Days 16 through 19.
Measure Participants	13
Part: B; Day 1; Treatment: Repaglinide Alone; Analyte: Repaglinide - AUC(0-t)	8.16 (13.7)
Part: B; Day 16; Treatment: Repaglinide with Tazemetostat; Analyte: Repaglinide - AUC(0-t)	14.7 (15.1)
Part: B; Day 1; Treatment: Repaglinide Alone; Analyte: Repaglinide - AUC(0-∞)	12.7 (19.4)
Part: B; Day 16; Treatment: Repaglinide with Tazemetostat; Analyte: Repaglinide - AUC(0-∞)	17 (15.7)

4. Primary Outcome

Title	Part B: Cmax of Repaglinide During Co-administration With Tazemetostat
Time Frame	Days 1 and 16, 0 to 8 hours post-dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part B
Arm/Group Description	Part B: Subjects enrolled in Part B will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg on Day 1. Administration of tazemetostat 800 mg BID will begin on Day 2. On Day 16, subjects again will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg approximately 1 hour after the morning dose of tazemetostat. Subjects also will receive omeprazole 20 mg once daily in the morning on Days 16 through 19.
Measure Participants	13
Part: B; Day 1; Treatment: Repaglinide Alone; Analyte: Repaglinide	5.14 (8.28)
Part: B; Day 16; Treatment: Repaglinide with Tazemetostat; Analyte: Repaglinide	7.75 (8.73)

5. Primary Outcome

Title	Part B: The Potential of Tazemetostat to Inhibit or Induce CYP2C19 Using Omeprazole as Probe a Substrate (AUC0-t, AUC0-∞)
Time Frame	Days 1 and 16, 0 to 8 hours post-dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part B
Arm/Group Description	Part B: Subjects enrolled in Part B will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg on Day 1. Administration of tazemetostat 800 mg BID will begin on Day 2. On Day 16, subjects again will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg approximately 1 hour after the morning dose of tazemetostat. Subjects also will receive omeprazole 20 mg once daily in the morning on Days 16 through 19.
Measure Participants	13
Part: B; Day 1; Treatment: Omeprazole Alone; Analyte: Omeprazole - AUC(0-t)	600 (1600)
Part: B; Day 16; Treatment: Omeprazole with Tazemetostat; Analyte: Omeprazole - AUC(0-t)	480 (837)
Part: B; Day 1; Treatment: Omeprazole Alone; Analyte: Omeprazole - AUC(0-∞)	672 (463)
Part: B; Day 16; Treatment: Omeprazole with Tazemetostat; Analyte: Omeprazole - AUC(0-∞)	1120 (1530)

6. Primary Outcome

Title	Part B: Cmax of Omeprazole During Co-administration With Tazemetostat
Time Frame	Days 1 and 16, 0 to 8 hours post-dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part B
Arm/Group Description	Part B: Subjects enrolled in Part B will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg on Day 1. Administration of tazemetostat 800 mg BID will begin on Day 2. On Day 16, subjects again will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg approximately 1 hour after the morning dose of tazemetostat. Subjects also will receive omeprazole 20 mg once daily in the morning on Days 16 through 19.
Measure Participants	13
Part: B; Day 1; Treatment: Omeprazole Alone; Analyte: Omeprazole	253 (462)
Part: B; Day 16; Treatment: Omeprazole with Tazemetostat; Analyte: Omeprazole	207 (275)

7. Primary Outcome

Title	Part B: Effect of Increased Gastric pH by Omeprazole on the PK of Tazemetostat (AUC0-t, AUC0-8)
Time Frame	Days 16 and 19, 0 to 8 hours post-dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part B
Arm/Group Description	Part B: Subjects enrolled in Part B will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg on Day 1. Administration of tazemetostat 800 mg BID will begin on Day 2. On Day 16, subjects again will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg approximately 1 hour after the morning dose of tazemetostat. Subjects also will receive omeprazole 20 mg once daily in the morning on Days 16 through 19.
Measure Participants	13
Part: B; Day 16; Treatment: Omeprazole with Tazemetostat; Analyte: EPZ-6438 - AUC(0-t)	1780 (2010)
Part: B; Day 19; Treatment: Tazemetostat Alone; Analyte: EPZ-6438 - AUC(0-t)	2150 (1030)

8. Primary Outcome

Title	Part B: Cmax of Tazemetostat During Co-administration With Omeprazole
Time Frame	Days 16 and 19, 0 to 8 hours post-dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part B
Arm/Group Description	Part B: Subjects enrolled in Part B will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg on Day 1. Administration of tazemetostat 800 mg BID will begin on Day 2. On Day 16, subjects again will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg approximately 1 hour after the morning dose of tazemetostat. Subjects also will receive omeprazole 20 mg once daily in the morning on Days 16 through 19.
Measure Participants	13
Part: B; Day 16; Treatment: Omeprazole with Tazemetostat; Analyte: EPZ-6438	521 (627)
Part: B; Day 19; Treatment: Tazemetostat Alone; Analyte: EPZ-6438	641 (404)

9. Secondary Outcome

Title	Incidence of Treatment-emergent Adverse Events as a Measure of Safety
Time Frame	From the first dose of study treatment until the earlier of either 30 days after the discontinuation of study treatment or until the initiation of subsequent anticancer therapy, up to 2 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Part A	Part B
Arm/Group Description	Subjects enrolled in Part A received treatment with oral tazemetostat tablets 400 mg twice daily for 24 days beginning on Day 1. Blood samples for the analysis of plasma tazemetostat and its metabolites concentrations were collected predose and over 8 hours after the morning dose of tazemetostat on Day 15. Subjects received fluconazole 400 mg once daily for 4 days starting on Day 16. On Day 19, blood samples for the analysis of plasma tazemetostat, its metabolites, and fluconazole were collected predose and over 8 hours after the morning tazemetostat dose. Tazemetostat 400 mg twice daily continued through Day 24. Subjects then received tazemetostat 800 mg twice daily starting on Day 25.	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.
Measure Participants	16	16
Any TEAE	12 75%	14 87.5%
Any TEAE Grade 3 or 4	7 43.8%	8 50%
Any Treatment-Related TEAE	9 56.3%	10 62.5%
Any Treatment-Related TEAE Grade 3 or 4	4 25%	3 18.8%
Any TEAE Leading to Dose Reduction	2 12.5%	2 12.5%
Any TEAE Leading to Study Drug Interruption	3 18.8%	6 37.5%
Any TEAE Leading to Study Drug Discontinuation	0 0%	0 0%
Any TESAE	4 25%	6 37.5%
Any Treatment-Related TESAE	1 6.3%	0 0%
Any Protocol Defined AE of Special Interest	0 0%	0 0%

10. Secondary Outcome

Title	Part A: PK of Tazemetostat and Its Metabolites After Administration Alone and With Fluconazole (AUC0-t, AUC0-8)
Time Frame	Days 15 and 19, 0 to 8 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Part A
Arm/Group Description	Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25.
Measure Participants	14
Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ-6930 (ER-897387)	2590 (1200)
Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ-6930 (ER-897387)	2860 (1600)
Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ006931	770 (630)
Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ006931	921 (780)
Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ034163	276 (415)
Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ034163	295 (430)

11. Secondary Outcome

Title	Part A: Tmax of Tazemetostat After Administration Alone and With Fluconazole
Time Frame	Days 15 and 19, 0 to 8 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Part A
Arm/Group Description	Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25.
Measure Participants	14
Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ-6438	1.13 (0.87)
Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ-6438	2 (0.84)

12. Secondary Outcome

Title	Part A: t1/2 of Tazemetostat After Administration Alone and With Fluconazole
Time Frame	Days 15 and 19, 0 to 8 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Part A
Arm/Group Description	Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25.
Measure Participants	14
Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ-6438	2.88 (0.491)
Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ-6438	3.56 (0.453)

13. Secondary Outcome

Title	Part A: Cmax of Tazemetostat Metabolites After Administration Alone and With Fluconazole
Time Frame	Days 15 and 19, 0 to 8 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Part A
Arm/Group Description	Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25.
Measure Participants	14
Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ-6930 (ER-897387)	629 (270)
Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ-6930 (ER-897387)	548 (288)
Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ006931	166 (105)
Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ006931	167 (153)
Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ034163	46 (56.7)
Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ034163	47.1 (61.4)

14. Secondary Outcome

Title	Part A: Tmax of Tazemetostat Metabolites After Administration Alone and With Fluconazole
Time Frame	Days 15 and 19, 0 to 8 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Part A
Arm/Group Description	Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25.
Measure Participants	14
Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ-6930 (ER-897387)	2.01 (0.65)
Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ-6930 (ER-897387)	2.02 (0.86)
Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ006931	2.01 (0.89)
Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ006931	2.47 (0.9)
Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ034163	2.02 (1.26)
Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ034163	2.02 (1.27)

15. Secondary Outcome

Title	Part A: t1/2 of Tazemetostat Metabolites After Administration Alone and With Fluconazole
Time Frame	Days 15 and 19, 0 to 8 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Part A
Arm/Group Description	Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25.
Measure Participants	14
Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ-6930 (ER-897387)	2.89 (0.358)
Part: A; Day 19; Treatment: Tazemetostat with Fluconazole; Analyte: EPZ-6930 (ER-897387)	3.92 (0.621)
Part: A; Day 15; Treatment: Tazemetostat Alone; Analyte: EPZ006931	3.24 (0.565)

16. Secondary Outcome

Title	Part A: Exposure of Fluconazole After Administration of 400 mg Once Daily for 4 Days (AUC0-8)
Time Frame	Day 19, 0 to 8 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Part A
Arm/Group Description	Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25.
Measure Participants	14
Geometric Mean (Standard Deviation) [h*ng/mL]	170000 (48300)

17. Secondary Outcome

Title	Part A: Cmax of Fluconazole After Administration of 400mg Once Daily for 4 Days
Time Frame	Day 19, 0 to 8 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Part A
Arm/Group Description	Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25.
Measure Participants	14
Geometric Mean (Standard Deviation) [ng/mL]	25900 (6500)

18. Secondary Outcome

Title	Part A: Tmax of Fluconazole After Administration of 400mg Once Daily for 4 Days
Time Frame	Day 19, 0 to 8 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Part A
Arm/Group Description	Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25.
Measure Participants	14
Median (Standard Deviation) [hours]	1.48 (1.95)

19. Secondary Outcome

Title	The Antitumor Activity of Tazemetostat Will be Assessed in Patients With Diffuse Large B-cell Lymphoma (DLBCL), Marginal Zone Lymphoma (MZL), Follicular Lymphoma (FL) or Advanced Solid Tumors .
Description	Objective response rate (ORR: complete response [CR] or PR) and disease control rate (DCR: CR or PR, or stable disease lasting 24 weeks or longer from start of treatment with tazemetostat) using Lugano Classification for subjects with lymphoma, or Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for subjects with solid tumors.
Time Frame	Within 28 days of Day 1, 8 weeks, 16 weeks, 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lymphoma	Advanced Solid Tumors
Arm/Group Description	Subjects with B-cell lymphomas	Subjects with Advanced Solid Tumors
Measure Participants	13	16
Complete response (CR)	1 6.3%	0 0%
Partial response (PR)	1 6.3%	2 12.5%
Stable disease (SD)	0 0%	9 56.3%
Progressive disease (PD)	2 12.5%	5 31.3%
Not evaluable, missing, or unknown	9 56.3%	3 18.8%
Objective Response Rate (ORR)	2 12.5%	2 12.5%
Disease control rate (DCR) at 24 weeks	2 12.5%	4 25%
Number of responders (achieving a CR or PR)	2 12.5%	2 12.5%

Adverse Events

Time Frame	Adverse Events were collected over a period of 2 years.
Arm/Group Title	Part A		Part B
Arm/Group Description	Part A: Subjects enrolled in Part A will receive treatment with oral tazemetostat tablets 400 mg BID for 24 days beginning on Day 1. Subjects will receive fluconazole 400 mg once daily for 4 days starting on Day 16. Tazemetostat 400 mg BID will continue through Day 24. Subjects will then receive tazemetostat 800 mg BID starting on Day 25.		Part B: Subjects enrolled in Part B will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg on Day 1. Administration of tazemetostat 800 mg BID will begin on Day 2. On Day 16, subjects again will receive single oral doses of repaglinide 0.25 mg and omeprazole 20 mg approximately 1 hour after the morning dose of tazemetostat. Subjects also will receive omeprazole 20 mg once daily in the morning on Days 16 through 19.
All Cause Mortality
	Part A		Part B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/16 (6.3%)		3/16 (18.8%)
Serious Adverse Events
	Part A		Part B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/16 (25%)		6/16 (37.5%)
Blood and lymphatic system disorders
Anaemia	0/16 (0%)		1/16 (6.3%)
Gastrointestinal disorders
Abdominal pain	2/16 (12.5%)		0/16 (0%)
Faecal incontinence	0/16 (0%)		1/16 (6.3%)
Small intestinal obstruction	0/16 (0%)		1/16 (6.3%)
Infections and infestations
Herpes zoster	1/16 (6.3%)		0/16 (0%)
Appendicitis	0/16 (0%)		1/16 (6.3%)
Bronchitis	0/16 (0%)		1/16 (6.3%)
Peritonitis bacterial	0/16 (0%)		1/16 (6.3%)
Sepsis	0/16 (0%)		1/16 (6.3%)
Injury, poisoning and procedural complications
Subdural haematoma	0/16 (0%)		1/16 (6.3%)
Investigations
Platelet count decreased	0/16 (0%)		1/16 (6.3%)
Metabolism and nutrition disorders
Hypercalcaemia	1/16 (6.3%)		0/16 (0%)
Hypocalcaemia	0/16 (0%)		1/16 (6.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	0/16 (0%)		1/16 (6.3%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	0/16 (0%)		1/16 (6.3%)
Pneumonia aspiration	0/16 (0%)		1/16 (6.3%)
Respiratory failure	0/16 (0%)		1/16 (6.3%)
Other (Not Including Serious) Adverse Events
	Part A		Part B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/16 (75%)		14/16 (87.5%)
Cardiac disorders
Angina pectoris	0/16 (0%)		1/16 (6.3%)
Stress cardiomyopathy	0/16 (0%)		1/16 (6.3%)
Ear and labyrinth disorders
Ear pain	0/16 (0%)		1/16 (6.3%)
Eye disorders
Diplopia	1/16 (6.3%)		0/16 (0%)
Ocular discomfort	1/16 (6.3%)		0/16 (0%)
Photophobia	1/16 (6.3%)		0/16 (0%)
Macular oedema	0/16 (0%)		1/16 (6.3%)
Visual acuity reduced	0/16 (0%)		1/16 (6.3%)
Gastrointestinal disorders
Nausea	6/16 (37.5%)		3/16 (18.8%)
Diarrhoea	4/16 (25%)		4/16 (25%)
Vomiting	4/16 (25%)		3/16 (18.8%)
Flatulence	2/16 (12.5%)		2/16 (12.5%)
Abdominal distension	1/16 (6.3%)		1/16 (6.3%)
Abdominal pain upper	1/16 (6.3%)		0/16 (0%)
Constipation	1/16 (6.3%)		4/16 (25%)
Eructation	1/16 (6.3%)		0/16 (0%)
Oral pain	1/16 (6.3%)		0/16 (0%)
Umbilical hernia	0/16 (0%)		1/16 (6.3%)
General disorders
Fatigue	6/16 (37.5%)		8/16 (50%)
Asthenia	1/16 (6.3%)		0/16 (0%)
Gait disturbance	1/16 (6.3%)		0/16 (0%)
Influenza like illness	1/16 (6.3%)		0/16 (0%)
Mucosal inflammation	1/16 (6.3%)		0/16 (0%)
Oedema peripheral	1/16 (6.3%)		0/16 (0%)
Face oedema	0/16 (0%)		1/16 (6.3%)
Generalised oedema	0/16 (0%)		1/16 (6.3%)
Pain	0/16 (0%)		1/16 (6.3%)
Pyrexia	0/16 (0%)		2/16 (12.5%)
Immune system disorders
Seasonal allergy	1/16 (6.3%)		0/16 (0%)
Infections and infestations
Upper respiratory tract infection	2/16 (12.5%)		2/16 (12.5%)
Fungal skin infection	1/16 (6.3%)		0/16 (0%)
Pneumonia	1/16 (6.3%)		2/16 (12.5%)
Viral rash	1/16 (6.3%)		0/16 (0%)
Lower respiratory tract infection	0/16 (0%)		1/16 (6.3%)
Osteomyelitis	0/16 (0%)		1/16 (6.3%)
Otitis media	0/16 (0%)		1/16 (6.3%)
Otitis media bacterial	0/16 (0%)		1/16 (6.3%)
Sinusitis	0/16 (0%)		2/16 (12.5%)
Injury, poisoning and procedural complications
Arthropod bite	1/16 (6.3%)		0/16 (0%)
Fall	1/16 (6.3%)		2/16 (12.5%)
Hip fracture	0/16 (0%)		1/16 (6.3%)
Incision site pain	0/16 (0%)		2/16 (12.5%)
Investigations
Blood creatinine increased	1/16 (6.3%)		0/16 (0%)
Blood alkaline phosphatase increased	0/16 (0%)		1/16 (6.3%)
Blood calcium decreased	0/16 (0%)		1/16 (6.3%)
Blood immunoglobulin G decreased	0/16 (0%)		1/16 (6.3%)
Ejection fraction decreased	0/16 (0%)		1/16 (6.3%)
Haemoglobin decreased	0/16 (0%)		1/16 (6.3%)
Lymphocyte count decreased	0/16 (0%)		1/16 (6.3%)
Neutrophil count decreased	0/16 (0%)		1/16 (6.3%)
Weight increased	0/16 (0%)		1/16 (6.3%)
White blood cell count decreased	0/16 (0%)		2/16 (12.5%)
Metabolism and nutrition disorders
Decreased appetite	1/16 (6.3%)		0/16 (0%)
Hypokalaemia	0/16 (0%)		1/16 (6.3%)
Hypomagnesaemia	0/16 (0%)		1/16 (6.3%)
Hyponatraemia	0/16 (0%)		1/16 (6.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/16 (6.3%)		0/16 (0%)
Arthritis	1/16 (6.3%)		0/16 (0%)
Back pain	1/16 (6.3%)		1/16 (6.3%)
Bone pain	1/16 (6.3%)		0/16 (0%)
Groin pain	1/16 (6.3%)		0/16 (0%)
Muscle spasms	1/16 (6.3%)		1/16 (6.3%)
Muscular weakness	1/16 (6.3%)		0/16 (0%)
Fracture pain	0/16 (0%)		1/16 (6.3%)
Pain in extremity	0/16 (0%)		1/16 (6.3%)
Nervous system disorders
Dizziness	3/16 (18.8%)		0/16 (0%)
Dysgeusia	2/16 (12.5%)		0/16 (0%)
Balance disorder	1/16 (6.3%)		0/16 (0%)
Headache	1/16 (6.3%)		0/16 (0%)
Brain compression	0/16 (0%)		1/16 (6.3%)
Neuropathy peripheral	0/16 (0%)		1/16 (6.3%)
Paraesthesia	0/16 (0%)		1/16 (6.3%)
Presyncope	0/16 (0%)		1/16 (6.3%)
Psychiatric disorders
Insomnia	2/16 (12.5%)		0/16 (0%)
Anxiety	1/16 (6.3%)		0/16 (0%)
Depression	1/16 (6.3%)		0/16 (0%)
Agitation	0/16 (0%)		1/16 (6.3%)
Renal and urinary disorders
Micturition urgency	0/16 (0%)		1/16 (6.3%)
Pollakiuria	0/16 (0%)		1/16 (6.3%)
Reproductive system and breast disorders
Testicular swelling	1/16 (6.3%)		0/16 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/16 (6.3%)		2/16 (12.5%)
Wheezing	1/16 (6.3%)		0/16 (0%)
Dyspnoea	0/16 (0%)		1/16 (6.3%)
Epistaxis	0/16 (0%)		1/16 (6.3%)
Haemoptysis	0/16 (0%)		1/16 (6.3%)
Nasal congestion	0/16 (0%)		2/16 (12.5%)
Oropharyngeal pain	0/16 (0%)		1/16 (6.3%)
Pulmonary pain	0/16 (0%)		1/16 (6.3%)
Skin and subcutaneous tissue disorders
Dermatitis acneiform	1/16 (6.3%)		0/16 (0%)
Dry skin	1/16 (6.3%)		0/16 (0%)
Skin exfoliation	1/16 (6.3%)		0/16 (0%)
Skin fissures	1/16 (6.3%)		0/16 (0%)
Skin lesion	1/16 (6.3%)		0/16 (0%)
Swelling face	1/16 (6.3%)		0/16 (0%)
Alopecia	0/16 (0%)		1/16 (6.3%)
Ecchymosis	0/16 (0%)		1/16 (6.3%)
Onychoclasis	0/16 (0%)		1/16 (6.3%)
Pruritus	0/16 (0%)		1/16 (6.3%)
Rash	0/16 (0%)		1/16 (6.3%)
Vascular disorders
Hypertension	1/16 (6.3%)		1/16 (6.3%)
Hot flush	0/16 (0%)		1/16 (6.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.