A Study to Investigate the Safety, Pharmacokinetics, Phar... | NCT02082977 | Trialant
NCT02082977
Sponsor
GlaxoSmithKline
Status
Terminated
Last Update Posted
Feb 25, 2020Actual
Enrollment
41Actual
Phase
Phase 1
Conditions
Cancer
Neoplasms
Interventions
GSK2816126
Countries
United States
France
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT02082977
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
117208
Secondary IDs
ID
Type
Description
Link
2013-001585-42
EudraCT Number
Brief Title
A Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK2816126 in Subjects With Relapsed/Refractory Diffuse Large B Cell Lymphoma, Transformed Follicular Lymphoma, Other Non-Hodgkin's Lymphomas, Solid Tumors and Multiple Myeloma
Official Title
A Phase I Open-label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK2816126 in Subjects With Relapsed/Refractory Diffuse Large B Cell Lymphoma, Transformed Follicular Lymphoma, Other Non-Hodgkin's Lymphomas, Solid Tumors and Multiple Myeloma
Acronym
Not provided
Organization
GlaxoSmithKlineINDUSTRY
Status Module
Record Verification Date
Feb 2020
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
The maximal dose and schedule attained with GSK2816126 has shown insufficient evidence of clinical activity, and does not justify further clinical investigation
Expanded Access Info
No
Start Date
Apr 24, 2014Actual
Primary Completion Date
Jun 20, 2017Actual
Completion Date
Jun 20, 2017Actual
First Submitted Date
Jan 16, 2014
First Submission Date that Met QC Criteria
Mar 6, 2014
First Posted Date
Mar 11, 2014Estimated
Results Waived
Not provided
Results First Submitted Date
Jun 7, 2018
Results First Submitted that Met QC Criteria
Apr 2, 2019
Results First Posted Date
Jun 28, 2019Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Feb 17, 2020
Last Update Posted Date
Feb 25, 2020Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
GlaxoSmithKlineINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This is an open-label, multicenter, 2-part study to determine the recommended Phase 2 dose (RP2D) for GSK2816126 given twice weekly by intravenous (IV) infusion. Part 1 will be conducted in adult subjects with relapsed/refractory diffuse large B cell lymphoma (DLBCL), transformed follicular lymphoma (tFL), other Non-Hodgkin's lymphomas (NHL), solid tumors (including castrate resistant prostate cancer) and multiple myeloma (MM) to determine the safety and tolerability of GSK2816126. Expansion cohorts (Part 2) are planned to further explore clinical activity of GSK2816126 at the RP2D in subjects with Enhancer of Zeste 2 (EZH2) wild type and EZH2 mutant positive germinal center B-cell like diffuse large B cell lymphoma (GCB-DLBCL), tFL and MM.
Detailed Description
Not provided
Conditions Module
Conditions
Cancer
Neoplasms
Keywords
Refractory
Phase I study, dose escalation study
diffuse large B cell lymphoma
Relapsed
Solid tumors
transformed follicular lymphoma
Multiple myeloma
GSK2816126
Non-Hodgkin's lymphoma
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
41Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Part 1:GSK2816126 50 mg twice-weekly
Experimental
Eligible subjects will receive GSK2816126 with a starting dose of 50 milligrams (mg) twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
Drug: GSK2816126
Part 1:GSK2816126 100 mg twice-weekly
Experimental
Eligible subjects will receive GSK2816126 with a dose of 100 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
Drug: GSK2816126
Part 1:GSK2816126 200 mg twice-weekly
Experimental
Eligible subjects will receive GSK2816126 with a dose of 200 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
Drug: GSK2816126
Part 1:GSK2816126 400 mg twice-weekly
Experimental
Eligible subjects will receive GSK2816126 with a dose of 400 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
Drug: GSK2816126
Part 1:GSK2816126 800 mg twice-weekly
Experimental
Eligible subjects will receive GSK2816126 with a dose of 800 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
Interventions
Name
Type
Description
Arm Group Labels
Other Names
GSK2816126
Drug
GSK2816126 will be supplied as a solution containing 15 milligram per milliliter (mg/mL) GSK2816126 in water for injection.
Part 1:GSK2816126 100 mg twice-weekly
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs)
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/ incapacity, is a congenital anomaly/ birth defect, other situations and is associated with liver injury or impaired liver function. The analysis was performed on All Subjects Population which included all participants who received at least one dose of study treatment.
Up to 3.2 years
Part 1: Number of Participants With Dose Limiting Toxicities (DLT)
An event was considered a DLT if it occurred within first 4 weeks (28 days) of treatment, and met the criteria's for hematologic , non-hematologic, infusion reactions and other toxicities, unless it can be clearly established that the event is unrelated to treatment.
Up to 4 weeks
Part 1: Number of Participants Withdrawn Due to AEs
A participant was considered to have completed the study if they have completed their end of study visit or if the participant died or was still in follow-up at the time the study was closed or terminated. Participants were monitored from start of the study till the development of toxicity. The data for number of participants withdrawn due to AEs have been presented.
Up to 3.2 years
Part 1: Number of Participants With Dose Interruptions
The number of participants who had any dose interruptions have been presented.
Up to 3.2 years
Part 1: Number of Participants With Dose Reductions
Secondary Outcomes
Measure
Description
Time Frame
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) Following Single and Repeat Dose Administration of GSK2816126
Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-t) following single (Day 1) and repeat dose (Day 15) administration of GSK2816126. Pharmacokinetic analysis of GSK2816126 in Part 1 was conducted by non-compartmental methods. The analysis was performed on Pharmacokinetic Population which included all participants in the All Subject population for whom a blood sample for pharmacokinetics was analyzed and at least 1 non-missing values was obtained. NA indicates data was not available since geometric coefficient of variation could not be calculated for single participant. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Part 1 Inclusion Criteria
Provided signed written informed consent
Males and females >=18 years of age (at the time consent is obtained).
Tumor type criteria: relapsed/refractory non-Hodgkin's lymphoma (NHL) that meets one of the following criteria:
Germinal Center B cell Diffuse large B cell lymphoma (GCB-DLBCL) relapsed or refractory to at least one prior regimen (e.g., rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone [R-CHOP]) AND not a candidate for standard salvage regimens or autologous or allogeneic stem cell transplant. Local confirmation of lymphoma subtype (e.g. GCB-DLBCL) is allowed for enrollment but must be confirmed through central laboratory testing.
Solid tumors that meet the following criteria: Measurable disease by Response Evaluation Criteria In Solid Tumors 1.1 (RECIST) in at least 1 site. For Castrate Resistant Prostate Cancer (CRPC) measurable disease can also include Prostate Specific Antigen (PSA) level. Disease progression with the last line of therapy and at least one prior standard of care regimens, or tumor for which there is no approved therapy, or for which standard therapy is unsuitable or refused. Mutation Status: Solid tumor types, other than prostate, must have a one of the following EZH2 inhibitor sensitizing mutations as determined via local testing: An activating mutation in EZH2 (Y641F/C/S/H/N, A677V/G, and/or A687V; Loss of a component of the SWI/SNF complex, including, but not limited to, ARID1A, SMARCB1 (aka SNF5/INI1/BAF47), SMARCA4 (aka BRG1), or PBRM1 (aka PB1) as determined by molecular testing (bi-allelic loss or mutation) or immunohistochemistry; Loss of BAP1 (ubiquitin carboxy-terminal hydrolase) as determined by molecular testing (bi-allelic loss or mutation) or immunohistochemistry
CRPC subjects: Must have measurable disease by either: RECIST1.1 or a minimum PSA of 5 nanogram/milliliter; Disease progression on last line of therapy and must have progressed on abiraterone, enzalutamide, or taxane chemotherapy; Subjects may continue GnRH agonists; Small cell prostate cancer is eligible
For all subjects: Availability of archival tissue, or willingness to undergo fresh biopsy if archival tissue is not available.
Must have a pre-existing central venous access such as a port, Hickmann catheter or a peripherally inserted central catheter (PICC line) or be willing and able to have one inserted.
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
Men with a female partner of childbearing potential must have either had a prior bilateral vasectomy with resultant azoospermia, bilateral orchiectomy, or must agree to use one of the contraception methods listed in protocol from the time of the first dose of study medication until at least 2 weeks (14 days) after the last dose of study treatment due to the long elimination phase of study drug.
A female subject is eligible to participate ifs she is of: Non-child bearing potential as described in the protocol; OR Child bearing potential and agrees to use effective contraception as described in the protocol, for an appropriate period of time (as determined by the product label) prior to the start of dosing to sufficiently minimize the risk of pregnancy and for at least 2 weeks (14 days) following the last dose of study treatment. Women of childbearing potential must have a negative serum pregnancy test within 7 days of first dose of study treatment followed by negative urine or serum pregnancy test once every 4 weeks (prior to next dose cycle) thereafter.- Adequate organ system function as defined in the protocol.
Part 2 Inclusion Criteria
In addition to inclusion criteria listed for Part 1, Part 2 will enroll GCB-DLBCL tFL and MM subjects only. Relapsed and/or refractory MM or tFL that have failed prior standard therapy and for which there is no standard salvage regimen
Lymphoma subjects will be required to undergo EZH2 mutation testing. This will require availability of archival tissue, or willingness to undergo fresh biopsy, for central testing of EZH2 mutation status.
Based on the results of the mutation test, lymphoma subjects may be enrolled in one of four cohorts: GCB-DLBCL EZH2 mutant cohort: Tumors must contain one, or more, of the following EZH2 activating mutations: Y641F; Y641N; Y641S; Y641H; Y641C; A677G; and/or A687V. GCB-DLBCL EZH2 wild type cohort: Tumors that do not contain one of the above mutations; Subjects with tumors harboring EZH2 mutations other than the seven outlined above will be enrolled in the EZH2 wild type cohort. tFL EZH2 mutant cohort: Tumors must contain one, or more, of the following EZH2 activating mutations: Y641F; Y641N; Y641S; Y641H; Y641C; A677G; and/or A687V. tFL EZH2 wild type cohort: Tumors that do not contain one of the above mutations; Subjects with tumors harboring EZH2 mutations other than the seven outlined above will be enrolled in the EZH2 wild type cohort
Part 1 and 2 Exclusion Criteria
Receiving any cancer therapy within 2 weeks of first dose (including surgery, and/or tumor embolization) Note: the following are allowed: Corticosteroids to control systemic or local symptoms, up to a dose of 10 mg prednisone or equivalent daily and stable for at least 7 days prior to enrollment. Subjects with prostate cancer may remain on GnRH agonists. Other hormonal therapies (e.g., bicalutamide, abiraterone and enzlutimide) for prostate cancer must be stopped 4 weeks prior to enrolment.
Note: the following are NOT allowed: Chemotherapy regimens with delayed toxicity within the last 3 weeks. Nitrogen mustards, Melphalan, Monoclonal antibody or Nitrosourea within the last 6 weeks.
Received an investigational anti-cancer drug within 6weeks, or within 5 half-lives (whichever is shorter) of the first dose of study drug(s). A minimum of 14 days must have passed between the last dose of prior investigational agent and the first dose of study drug.
Current use of a prohibited medication per protocol or expected to require any of these medications during treatment with study drug.
Known Human Immunodeficiency Virus, or serological evidence for Hepatitis B (positive hepatitis B surface antigen [HBsAg]), or chronic Hepatitis C infection. For subjects who are negative for HBsAg, but Hepatitis B core Antibody [HBcAB] positive, a HBV DNA (viral load) test will be performed and if negative are eligible. Subjects with positive Hepatitis C antibody serology with a negative HCV ribonucleic acid (RNA) test results are eligible.
Concurrent use of therapeutic warfarin is allowed. However, anticoagulants that do not have reversal agents available are prohibited.
Any major surgery, radiotherapy or immunotherapy within the 4 weeks prior to first dose of study drug, or palliative radiotherapy to a single symptomatic lesion within the 2 weeks prior to first dose of study drugs.
Subjects with prior allogeneic transplant are excluded: however, subjects who have previously received an autologous stem cell transplant are allowed if a minimum of 100 days has elapsed from the time of transplant and the subject has recovered from transplant-associated toxicities prior to the first dose of GSK2816126
Unresolved toxicity greater than Grade 1 National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4 from previous anti-cancer therapy, with the exception of alopecia and peripheral neuropathy. Lymphoma subjects with <= Grade 3 lymphopenia can be enrolled at the discretion of the investigator.
Packed red blood cell or platelet transfusion within 7 days of screening laboratory tests.
Psychological, familial, sociological or geographical conditions that do not permit compliance with the protocol.
Cardiac exclusion criteria: History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within the past 6 months prior to first dose of study drug; QTcF> 450 milliseconds (msec); Uncontrolled arrhythmias. Subjects with rate controlled atrial fibrillation for >1 month prior to first dose of study drug may be eligible; Class II, III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug or their excipients.
Pregnant or lactating female.
Unwillingness or inability to follow the procedures outlined in the protocol.
Uncontrolled diabetes or other medical condition that may interfere with assessment of toxicity.
Central nervous system (CNS) metastases, with the following exception: Subjects who have previously treated CNS metastases, are asymptomatic, and have no requirement for steroids at least 14 days prior to first dose of study drug; Subjects with carcinomatous meningitis are excluded regardless of clinical stability.
Invasive malignancy or history of invasive malignancy other than disease under study: any other invasive malignancy from which the subject has been disease-free for more than 2 years and, in the opinion of the principal investigator and GSK Medical Monitor, will not affect the evaluation of the effects of this clinical trial treatment on currently targeted malignancy, can be included in this clinical trial; Curatively treated non-melanoma skin cancer and any carcinoma-in-situ.
Yap TA, Winter JN, Giulino-Roth L, Longley J, Lopez J, Michot JM, Leonard JP, Ribrag V, McCabe MT, Creasy CL, Stern M, Pene Dumitrescu T, Wang X, Frey S, Carver J, Horner T, Oh C, Khaled A, Dhar A, Johnson PWM. Phase I Study of the Novel Enhancer of Zeste Homolog 2 (EZH2) Inhibitor GSK2816126 in Patients with Advanced Hematologic and Solid Tumors. Clin Cancer Res. 2019 Dec 15;25(24):7331-7339. doi: 10.1158/1078-0432.CCR-18-4121. Epub 2019 Aug 30.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
Plan to Share IPD
Yes
Description
IPD for this study will be made available via the Clinical Study Data Request site.
Types
Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame
IPD is available via the Clinical Study Data Request site (click on the link provided below)
Access Criteria
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
This study was terminated prior to the completion of Part 1 due to an unfavorable benefit risk profile. Part 2 was not conducted. Approximately 42 participants screened, of which 41 were treated in Part 1 including 20 participants with lymphoma and 21 with solid tumors, of these 22 completed, 5 died and 14 participants were withdrawn.
Recruitment Details
This was a 2-part study in participants with relapsed/refractory diffuse large B cell lymphoma, transformed follicular lymphoma, other Non-Hodgkin's lymphomas, solid tumors and multiple myeloma (MM). In Part 1 dose escalation, participants received 50 to 3000 milligrams (mg) of GSK2816126, and Part 2 was dose expansion.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Part 1:GSK2816126 50 mg Twice-weekly
Eligible participants received GSK2816126 with a starting dose of 50 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
FG001
Part 1:GSK2816126 100 mg Twice-weekly
Periods
Title
Milestones
Reasons Not Completed
Part 1 (Up to 3.2 Years)
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
SAP
No
Yes
No
Statistical Analysis Plan
Mar 1, 2018
Apr 25, 2018
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Non-Randomized
Intervention Model
Sequential Assignment
Intervention Model Description
Subjects will receive escalating doses of GSK2816126 in Part 1 of the study. Subjects enrolled in Part 2 will receive recommended Phase II dose (RP2D) based on Part 1 of the study.
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
This will be an open-label study. Hence, there will be no masking.
Who Masked
Not provided
Drug: GSK2816126
Part 1:GSK2816126 1200 mg twice-weekly
Experimental
Eligible subjects will receive GSK2816126 with a dose of 1200 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
Drug: GSK2816126
Part 1:GSK2816126 1800 mg twice-weekly
Experimental
Eligible subjects will receive GSK2816126 with a dose of 1800 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
Drug: GSK2816126
Part 1:GSK2816126 2400 mg twice-weekly
Experimental
Eligible subjects will receive GSK2816126 with a dose of 2400 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
Drug: GSK2816126
Part 1:GSK2816126 3000 mg twice-weekly
Experimental
Eligible subjects will receive GSK2816126 with a dose of 3000 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
Drug: GSK2816126
Part 2: All subjects
Experimental
Subjects with Germinal Center B-cell-like Diffuse Large B-cell Lymphoma (GCB-DLBCL)-mutant and wild type, Transformed Follicular Lymphoma (TFL)-mutant and wild type as well as with multiple myeloma (MM) will be enrolled in Part 2 of the study. Subjects enrolled in Part 2 will receive recommended Phase II dose (RP2D).
Drug: GSK2816126
Part 1:GSK2816126 1200 mg twice-weekly
Part 1:GSK2816126 1800 mg twice-weekly
Part 1:GSK2816126 200 mg twice-weekly
Part 1:GSK2816126 2400 mg twice-weekly
Part 1:GSK2816126 3000 mg twice-weekly
Part 1:GSK2816126 400 mg twice-weekly
Part 1:GSK2816126 50 mg twice-weekly
Part 1:GSK2816126 800 mg twice-weekly
Part 2: All subjects
The number of participants who had any dose reductions have been presented.
Up to 3.2 years
Part 1: Number of Participants With Worst Case Change From Baseline in Clinical Chemistry Parameters
Blood samples were collected for evaluation of clinical chemistry parameters including direct bilirubin, chloride, lactate dehydrogenase (LDH), total protein, urea/blood urea nitrogen (BUN) and uric acid. Baseline value was defined as the most recent, non-missing value from a local laboratory prior to the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. The summaries of worst case change from Baseline with respect to normal range have been presented for only those laboratory tests that are not gradable by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The number of participants with decreases to low, changes to normal or no changes from Baseline, and increases to high values have been presented. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Baseline and up to 3.2 years
Part 1: Number of Participants With Worst Case Change From Baseline in Hematology Parameters
Blood samples were collected for the analysis of hematology parameters including basophils, eosinophils, hematocrit, mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), monocytes, segmented (seg) neutrophils, red blood cell (RBC) count and reticulocytes. Baseline value was defined as the most recent, non-missing value from a local laboratory prior to the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. The summaries of worst case change from Baseline with respect to normal range have been presented for only those laboratory tests that are not gradable by CTCAE version 4.0. The number of participants with decreases to low, changes to normal or no changes from Baseline, and increases to high values have been presented. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Baseline and up to 3.2 years
Part 1:Number of Participants With Abnormal Values for Vital Signs
Vital sign measurements includes systolic blood pressure (SBP), diastolic blood pressure (DBP), body temperature and heart rate. Vital signs were measured after resting for at least 5 minutes in a semi-supine position. The number of participants with abnormal findings for vital signs have been presented.
Up to 3.2 years
Part 1: Number of Participants With Abnormal Findings for Electrocardiogram (ECG) Parameters
Single measurements of 12-lead ECGs were obtained a semi-recumbent or semi-supine position after at least a 5 minutes rest using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and corrected QT (QTc) intervals. The number of participants with abnormal, abnormal-not clinically significant (NCS), and abnormal-clinically significant (CS) worst case Post Baseline findings have been presented.
Up to 3.2 years
Part 2: Percentage of Participants Achieving Overall Response Rate
Overall response rate is defined as percentage of participants achieving complete response and partial response per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Up to 3.2 years
Pre-dose, 0.5, 1, 2, (12, 18 on Day 1 only), 24, and 96 hours post-dose from start of infusion; 0.5, 1, 2, 4, 6 hours from end of infusion on Cycle 1 of Day 1 and Day 15 (Each cycle was of 28 days)
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK2816126
Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-infinity) following single (Day 1) dose administration of GSK2816126. Pharmacokinetic analysis of GSK2816126 in Part 1 was conducted by non-compartmental methods. NA indicates data was not available since geometric coefficient of variation could not be calculated for single participant. Pharmacokinetic parameter derivation for some participants did not strictly conform to the prescribed acceptance criteria and hence data was not available for those participants.
Pre-dose, 0.5, 1, 2, 12, 18 , 24, and 96 hours post-dose from start of infusion; 0.5, 1, 2, 4, 6 hours from end of infusion on Cycle 1 of Day 1 (Each cycle was of 28 days)
Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK2816126
Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-tau) following repeat (Day 15) dose administration of GSK2816126. Pharmacokinetic analysis of GSK2816126 in Part 1 was conducted by non-compartmental methods. NA indicates data was not available since geometric coefficient of variation could not be calculated for single participant.
Pre-dose, 0.5, 1, 2, 24, and 96 hours post-dose from start of infusion; 0.5, 1, 2, 4, 6 hours from end of infusion on Cycle 1 of Day 15 (Each cycle was of 28 days)
Part 1: Trough (Pre-dose) Concentration at the End of Dosing Interval on the Specified Days (Ctau) Following Administration of GSK2816126
Blood samples were collected from participants for pharmacokinetic analysis including Ctau following specified days (Days 8 and 15) administration of GSK2816126. Pharmacokinetic analysis of GSK2816126 in Part 1 was conducted by non-compartmental methods. NA indicates data was not available as data could not be calculated due to limited number of participants at specified data point. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Pre-dose from start of infusion till end of infusion on Cycle 1 of Day 8; Pre-dose, 0.5, 1, 2, 24, and 96 hours post-dose from start of infusion; 0.5, 1, 2, 4, 6 hours from end of infusion on Cycle 1 of Day 15 (Each cycle was of 28 days)
Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2816126
Blood samples were collected from participants for pharmacokinetic analysis including Cmax following single (Day 1) and repeat dose (Day 15) administration of GSK2816126. Pharmacokinetic analysis of GSK2816126 in Part 1 was conducted by non-compartmental methods. NA indicates data was not available since geometric coefficient of variation could not be calculated for single participant. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Pre-dose, 0.5, 1, 2, (12, 18 on Day 1 only), 24, and 96 hours post-dose from start of infusion; 0.5, 1, 2, 4, 6 hours from end of infusion on Cycle 1 of Day 1 and Day 15 (Each cycle was of 28 days)
Part 1: Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of GSK2816126
Blood samples were collected from participants for pharmacokinetic analysis including Tmax following single (Day 1) and repeat dose (Day 15) administration of GSK2816126. Tmax is the time to reach Cmax, determined directly from the concentration-time data. Pharmacokinetic analysis of GSK2816126 in Part 1 was conducted by non-compartmental methods. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Pre-dose, 0.5, 1, 2, (12, 18 on Day 1 only), 24, and 96 hours post-dose from start of infusion; 0.5, 1, 2, 4, 6 hours from end of infusion on Cycle 1 of Day 1 and Day 15 (Each cycle was of 28 days)
Part 1: Apparent Terminal Phase Elimination Rate Constant (Lambda z) Following Single and Repeat Dose Administration of GSK2816126
Blood samples were collected from participants for pharmacokinetic analysis including lambda z following single (Day 1) and repeat dose (Day 15) administration of GSK2816126. Pharmacokinetic analysis of GSK2816126 in Part 1 was conducted by non-compartmental methods. Pharmacokinetic parameter derivation for some participants did not strictly conform to the prescribed acceptance criteria and hence data was not available for those participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Pre-dose, 0.5, 1, 2, (12, 18 on Day 1 only), 24, and 96 hours post-dose from start of infusion; 0.5, 1, 2, 4, 6 hours from end of infusion on Cycle 1 of Day 1 and Day 15 (Each cycle was of 28 days)
Part 1: Apparent Terminal Phase Half-life (T1/2) Following Single and Repeat Dose Administration of GSK2816126
Blood samples were collected from participants for pharmacokinetic analysis including T1/2 following single (Day 1) and repeat dose (Day 15) administration of GSK2816126. Pharmacokinetic analysis of GSK2816126 in Part 1 was conducted by non-compartmental methods. Pharmacokinetic parameter derivation for some participants did not strictly conform to the prescribed acceptance criteria and hence data was not available for those participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Pre-dose, 0.5, 1, 2, (12, 18 on Day 1 only), 24, and 96 hours post-dose from start of infusion; 0.5, 1, 2, 4, 6 hours from end of infusion on Cycle 1 of Day 1 and Day 15 (Each cycle was of 28 days)
Part 1: Accumulation Ratio Following Administration of GSK2816126
Accumulation ratio was determined from the ratio of AUC (0-tau) on Cycle 1 Day 15/AUC (0-tau) on Cycle 1 Day 1 by dose cohort. Only those participants with data available at the specified data points were analyzed. To assess accumulation ratio for a dose level based on ANOVA method, it was required that at least 2 participants had derived PK parameter AUC(0- tau) on both Cycle 1 Day 1 and Cycle 1 Day 15. For dose 100mg, 200mg and 400mg, only 1 participant received treatment. For dose 50mg, 2 participants received treatment but there was one participant whose AUC(0- tau) on Cycle 1 Day 15 could not be derived due to discontinuation of treatment before Day 15. Hence, accumulation ratio could not be calculated for these 4 arms. Accumulation ratio of GSK2816126 was estimated by calculating the ratio of geometric least squares (GLS) means of the AUC between Day 15 and Day 1 for all dose levels and corresponding 90 percent (%) confidence interval (CI) for each ratio.
Pre-dose, 0.5, 1, 2, (12, 18 on Day 1 only), 24, and 96 hours post-dose from start of infusion; 0.5, 1, 2, 4, 6 hours from end of infusion on Cycle 1 of Day 1 and Day 15 (Each cycle was of 28 days)
Part 1: Time Invariance Ratio Following Administration of GSK2816126
Ratio of AUC(0-tau) on Day15/Day1 AUC(0-inf) was calculated to assess time invariance. Only those participants with data available at specified data points were analyzed. To assess time invariance based on ANOVA method, it is required that at least 2 participants in a dose level had AUC(0-inf) on Cycle1 Day1 and AUC(0-tau) on Cycle1 Day15. For dose 100mg, 200mg and 400mg, only 1 participant received treatment. For 50mg, 2 participants received treatment but there was one participant whose AUC(0-tau) on Cycle1 Day15 could not be derived due to discontinuation of treatment before Day15, so time invariance could not be calculated. For 1200mg, 4 participants received treatment, however, AUC(0-inf) derivation on Cycle1 Day1 for 3 out of 4 participants did not strictly conform to the prescribed acceptance criteria. Time invariance ratio of GSK2816126 was estimated by calculating ratio of GLS means of AUC between Day15 and Day1 for all dose levels and corresponding 90% CI for each ratio.
Pre-dose, 0.5, 1, 2, (12, 18 on Day 1 only), 24, and 96 hours post-dose from start of infusion; 0.5, 1, 2, 4, 6 hours from end of infusion on Cycle 1 of Day 1 and Day 15 (Each cycle was of 28 days)
Part 1: Exposure Producing 50 Percent of the Maximum Effect (EC50) of GSK2816126 With Respect to Exposure Markers
The pharmacokinetic/pharmacodynamic relationship between GSK2816126 exposure markers (dose, concentration, Cmax or AUC) was planned to be characterized by linear and/or non-linear mixed effect models. This analysis was planned to be based on Pharmacodynamic Population which consists of participants in the All Subjects population for whom a pharmacodynamics/biomarkers sample was obtained and analyzed. This analysis was planned but not performed as the pharmacodynamic response was not observed and therefore a relationship between pharmacokinetic and pharmacodynamic parameters could not be determined.
Up to 3.2 years
Part 1: Maximum Effect (Emax) of GSK2816126 With Respect to Exposure Markers
The pharmacokinetic/pharmacodynamic relationship between GSK2816126 exposure markers (dose, concentration, Cmax or AUC) was characterized by linear and/or non-linear mixed effect models. This analysis was planned but not performed as the pharmacodynamic response was not observed and therefore a relationship between pharmacokinetic and pharmacodynamic parameters could not be determined.
Up to 3.2 years
Part 1: Number of Participants With Overall Change in Tri-methylated Histone H3 Lysine 27 (H3K27me3) Ratios Compared to Baseline
The pre and post-treatment samples for tumor or surrogate tissue/body fluid (e.g. Peripheral blood mononuclear cell [PBMCs], blood, skin or hair) were collected for the analysis of H3K27me3. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline was defined as any visit value minus Baseline value.
Baseline and up to 3.2 years
Part 1: Percentage of Participants With Solid Tumors Achieving Best Overall Response Rate
Overall response rate is defined as percentage of participants achieving complete response and partial response per RECIST version 1.1. Complete Response is the disappearance of all target/non-target lesions. Partial Response is at least a 30 percent decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence. The percentage of participants with solid tumors (including prostate) achieving best overall response rate have been presented. No participants with solid tumors were treated at doses below 800mg (i.e. 50mg, 100mg, 200mg, 400mg). Hence data could not be calculated for these 4 arms.
Up to 3.2 years
Part 1: Percentage of Participants With Lymphoma Achieving Best Overall Response Rate
Overall response rate is defined as percentage of participants achieving complete response and partial response per RECIST version 1.1. Complete Response is the disappearance of all target/non-target lesions. Partial Response is at least a 30 percent decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence. The percentage of participants with lymphoma achieving best overall response rate have been presented.
Up to 3.2 years
Part 1: Concentration of GSK2816126 and Its Metabolites in Blood
Blood samples were planned to be collected from participants in the pharmacokinetic/pharmacodynamic expansion cohort for analysis of GSK2816126 and its metabolites. Samples were not collected due to early termination of the study; therefore, no analysis could be performed.
Pre-dose, 0.5, 1, 2, (12, 18 on Day 1 only), 24, and 96 hours post-dose from start of infusion; 0.5, 1, 2, 4, 6 hours from end of infusion on Cycle 1 of Day 1 and Day 15 (Each cycle was of 28 days)
Part 1: Concentration of GSK2816126 and Its Metabolites in Bile
Bile samples were planned to be collected from participants in the pharmacokinetic/pharmacodynamic expansion cohort for analysis of GSK2816126 and its metabolites via the Entero-Test. Samples were not collected due to early termination of the study; therefore, no analysis could be performed.
Day 15
Part 1: Concentration of GSK2816126 and Its Metabolites in Urine
Urine samples were planned to be collected from participants in the pharmacokinetic/pharmacodynamic expansion cohort for analysis of GSK2816126 and its metabolites. Samples were not collected due to early termination of the study; therefore, no analysis could be performed.
Pre-dose and 0 to 24 hours post-dose on Day 1; 0 to 8 hours post-dose on Day 15
Part 1:Concentration of GSK2816126 in Urine After Dosing at Steady State
The amount of GSK2816126 excreted in urine after dosing at steady state was determined. The concentration of GSK2816126 in urine was planned to be measured with an investigational bio-analytical method and extrapolated to total amount excreted in urine over time using urine volume. Samples were not collected due to early termination of the study; therefore, no analysis could be performed.
Pre-dose and 0 to 24 hours post-dose on Day 1; 0 to 8 hours post-dose on Day 15
Part 2: Number of Participants With SAEs and Non-SAEs
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/ incapacity, is a congenital anomaly/ birth defect, other situations and is associated with liver injury or impaired liver function. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Up to 3.2 years
Part 2: Number of Participants With DLTs
An event was considered a DLT if it occurred within first 4 weeks (28 days) of treatment, and met the criteria's for hematologic , non-hematologic, infusion reactions and other toxicities, unless it can be clearly established that the event is unrelated to treatment. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Up to 4 weeks
Part 2: Number of Participants Withdrawn Due to AEs
A participant was considered to have completed the study if they have completed their end of study visit or if the participant died or was still in follow-up at the time the study was closed or terminated. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Up to 3.2 years
Part 2: Number of Participants With Dose Interruptions
The number of participants who had any dose interruptions were planned to be analyzed. However, this analysis was not performed for Part 2 as the study was terminated early during Part 1.
Up to 3.2 years
Part 2: Number of Participants With Dose Reductions
The number of participants who had any dose reduction or delay were planned to be analyzed. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Up to 3.2 years
Part 2: Number of Participants With Worst Case Change From Baseline in Clinical Chemistry Parameters
Blood samples were planned to be collected for evaluation of clinical chemistry parameters including direct bilirubin, chloride, LDH, total protein, urea/BUN and uric acid. Baseline value was defined as the most recent, non-missing value from a local laboratory prior to the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Baseline and up to 3.2 years
Part 2: Number of Participants With Worst Case Changes From Baseline in Hematology Parameters
Blood samples were planned to be collected for the analysis of hematology parameters including basophils, eosinophils, hematocrit, MCHC, MCH, MCV, monocytes, seg neutrophils, RBC count and reticulocytes. Baseline value was defined as the most recent, non-missing value from a local laboratory prior to the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Baseline and up to 3.2 years
Part 2: Number of Participants With Abnormal Values for Vital Signs
Vital sign measurements includes SBP, DBP, body temperature and heart rate. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Up to 3.2 years
Part 2: Number of Participants With Abnormal Findings for ECG Parameters
Single measurements of 12-lead ECGs were planned to be obtained a semi-recumbent or semi-supine position after at least a 5 minutes rest using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QTc intervals. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Up to 3.2 years
Part 2: Clearance Following Administration of GSK2816126
Blood samples were planned to be collected at Pre-dose, single draw between 0.5 and 1.9 hours from start of infusion, single draw between 3-6 hours following end of infusion on Day 1 and Day 11; Pre-dose on Day 4; Day 8, Day 11; Pre-dose on Day 15 for Cycle 1 and Cycles 2, 4, 6 and 12 pre-dose and within 5 minutes prior to end of infusion on Day 4 for population pharmacokinetic analysis of GSK2816126 including clearance. Each cycle was of 28 days. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Up to 3.2 years
Part 2: Volume of Distribution Following Administration of GSK2816126
Blood samples were planned to be collected on Pre-dose, single draw between 0.5 and 1.9 hours from start of infusion, single draw between 3-6 hours following end of infusion on Day 1 and Day 11; Pre-dose on Day 4; Day 8,Day 11; Pre-dose on Day 15 for Cycle 1 and Cycle 2, 4, 6 and 12 pre-dose and within 5 minutes prior to end of infusion on Day 4 for population pharmacokinetic analysis of GSK2816126 including clearance. Each cycle was of 28 days. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Up to 3.2 years
Part 2:EC50 of GSK2816126 With Respect to Exposure Markers
The pharmacokinetic/pharmacodynamic relationship between GSK2816126 exposure markers (dose, concentration, Cmax or AUC) was planned to be characterized by linear and/or non-linear mixed effect models. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Up to 3.2 years
Part 2:Emax of GSK2816126 With Respect to Exposure Markers
The pharmacokinetic/pharmacodynamic relationship between GSK2816126 exposure markers (dose, concentration, Cmax or AUC) was planned to be characterized by linear and/or non-linear mixed effect models. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Up to 3.2 years
Part 2: Number of Participants With Change in H3K27me3 Ratios Compared to Baseline
The pre and post-treatment samples for tumor or surrogate tissue/body fluid (e.g. PBMCs, blood, skin or hair) were planned to be collected for the analysis of H3K27me3. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline was defined as any visit value minus Baseline value. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Baseline and up to 3.2 years
Part 2: Concentration of GSK2816126 and Its Metabolites in Blood
Blood samples were planned to be collected from participants in the pharmacokinetic/pharmacodynamic expansion cohort for analysis of GSK2816126 and its metabolites. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Pre-dose, single draw between 0.5 and 1.9 hours from start of infusion, single draw between 3-6 hours following end of infusion on Day 1; Pre-dose on Day 15 for Cycle 1 and Cycles 2, 4, 6 and 12 (Each cycle was of 28 days)
Part 2: Concentration of GSK2816126 and Its Metabolites in Bile
Bile samples were planned to be collected from participants in the pharmacokinetic/pharmacodynamic expansion cohort for analysis of GSK2816126 and its metabolites via the Entero-Test. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Day 15
Part 2: Concentration of GSK2816126 and Its Metabolites in Urine
Urine samples were planned to be collected from participants in the pharmacokinetic/pharmacodynamic expansion cohort for analysis of GSK2816126 and its metabolites. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Pre-dose and 0 to 24 hours post-dose on Day 1; 0 to 8 hours post-dose on Day 15
Part 2:Concentration of GSK2816126 in Urine After Dosing at Steady State
The amount of GSK2816126 excreted in urine after dosing at steady state was planned to be determined. The concentration of GSK2816126 in urine was planned to be measured with an investigational bio-analytical method and extrapolated to total amount excreted in urine over time using urine volume. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Pre-dose and 0 to 24 hours post-dose on Day 1; 0 to 8 hours post-dose on Day 15
Part 2: Change in 4-beta-hydroxy Cholesterol to Cholesterol Ratio From Baseline Following Repeat Dosing of GSK2816126
Plasma analysis for 4-beta-hydroxycholesterol and cholesterol was planned to be conducted. Baseline value was defined as the most recent, non-missing value from a local laboratory prior to the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Baseline and up to 21 days
Part 2: Duration of Response
Duration of response for participants is defined as the time from the first documented evidence of a PR or CR until the first documented sign of disease progression or death due to any cause. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Up to 3.2 years
Part 2: Number of Participants With Progression Free Survival
PFS is defined as the interval between the first dose of study medication and the earliest date of disease progression or death due to any cause. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Up to 3.2 years
New York
New York
10021
United States
GSK Investigational Site
Villejuif
94805
France
GSK Investigational Site
Sutton
Surrey
SM2 5PT
United Kingdom
GSK Investigational Site
Southampton
SO16 6YD
United Kingdom
Eligible participants received GSK2816126 with a dose of 100 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
FG002
Part 1:GSK2816126 200 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 200 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
FG003
Part 1:GSK2816126 400 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 400 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
FG004
Part 1:GSK2816126 800 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 800 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
FG005
Part 1:GSK2816126 1200 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 1200 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
FG006
Part 1:GSK2816126 1800 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 1800 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
FG007
Part 1:GSK2816126 2400 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 2400 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
FG008
Part 1:GSK2816126 3000 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 3000 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
FG009
Part 2: All Participants
Participants with Germinal Center B-cell-like Diffuse Large B-cell Lymphoma (GCB-DLBCL)-mutant and wild type, Transformed Follicular Lymphoma (TFL)-mutant and wild type as well as with MM were planned to be enrolled in Part 2 of the study. Participants enrolled in Part 2 were planned to receive recommended Phase II dose (RP2D).
FG0002 subjects
FG0011 subjects
FG0021 subjects
FG0031 subjects
FG0043 subjects
FG0054 subjects
FG00610 subjects
FG00712 subjects
FG0087 subjects
FG0090 subjects
COMPLETED
FG0001 subjects
FG0011 subjects
FG0021 subjects
FG0031 subjects
FG0042 subjects
FG0051 subjects
FG0064 subjects
FG0077 subjects
FG0084 subjects
FG0090 subjects
NOT COMPLETED
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0041 subjects
FG0053 subjects
FG0066 subjects
FG0075 subjects
FG0083 subjects
FG0090 subjects
Type
Comment
Reasons
Death
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0051 subjects
FG0062 subjects
FG0070 subjects
FG0081 subjects
FG0090 subjects
Study closed/terminated
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Physician Decision
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Withdrawal by Subject
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Part 2 (Up to 3.2 Years)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Data was not collected in Part 2 of the study as no participant was enrolled in Part 2.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Part 1:GSK2816126 50 mg Twice-weekly
Eligible participants received GSK2816126 with a starting dose of 50 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
BG001
Part 1:GSK2816126 100 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 100 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
BG002
Part 1:GSK2816126 200 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 200 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
BG003
Part 1:GSK2816126 400 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 400 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
BG004
Part 1:GSK2816126 800 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 800 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
BG005
Part 1:GSK2816126 1200 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 1200 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
BG006
Part 1:GSK2816126 1800 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 1800 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
BG007
Part 1:GSK2816126 2400 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 2400 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
BG008
Part 1:GSK2816126 3000 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 3000 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
BG009
Part 2: All Participants
Participants with Germinal Center B-cell-like Diffuse Large B-cell Lymphoma (GCB-DLBCL)-mutant and wild type, Transformed Follicular Lymphoma (TFL)-mutant and wild type as well as with MM were planned to be enrolled in Part 2 of the study. Participants enrolled in Part 2 were planned to receive recommended Phase II dose (RP2D) .
BG010
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0002
BG0011
BG0021
BG0031
BG0043
BG0054
BG00610
BG00712
BG0087
BG0090
BG01041
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG00044.0± 12.73
BG00154.0± NANA indicates data was not available as standard deviation could not be calculated for single participant.
BG00256.0± NA
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0000
BG0010
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
African American/African Heritage
BG0000
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs)
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/ incapacity, is a congenital anomaly/ birth defect, other situations and is associated with liver injury or impaired liver function. The analysis was performed on All Subjects Population which included all participants who received at least one dose of study treatment.
All Subjects Population
Posted
Number
Participants
Up to 3.2 years
ID
Title
Description
OG000
Part 1:GSK2816126 50 mg Twice-weekly
Eligible participants received GSK2816126 with a starting dose of 50 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG001
Part 1:GSK2816126 100 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 100 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG002
Part 1:GSK2816126 200 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 200 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG003
Part 1:GSK2816126 400 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 400 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG004
Part 1:GSK2816126 800 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 800 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG005
Part 1:GSK2816126 1200 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 1200 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG006
Part 1:GSK2816126 1800 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 1800 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG007
Part 1:GSK2816126 2400 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 2400 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG008
Part 1:GSK2816126 3000 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 3000 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
Units
Counts
Participants
OG0002
OG0011
OG0021
OG003
Title
Denominators
Categories
Any Non-SAE
Title
Measurements
OG0002
OG0011
OG0021
OG003
Primary
Part 1: Number of Participants With Dose Limiting Toxicities (DLT)
An event was considered a DLT if it occurred within first 4 weeks (28 days) of treatment, and met the criteria's for hematologic , non-hematologic, infusion reactions and other toxicities, unless it can be clearly established that the event is unrelated to treatment.
All Subjects Population
Posted
Number
Participants
Up to 4 weeks
ID
Title
Description
OG000
Part 1:GSK2816126 50 mg Twice-weekly
Eligible participants received GSK2816126 with a starting dose of 50 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG001
Part 1:GSK2816126 100 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 100 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG002
Part 1:GSK2816126 200 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 200 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG003
Part 1:GSK2816126 400 mg Twice-weekly
Primary
Part 1: Number of Participants Withdrawn Due to AEs
A participant was considered to have completed the study if they have completed their end of study visit or if the participant died or was still in follow-up at the time the study was closed or terminated. Participants were monitored from start of the study till the development of toxicity. The data for number of participants withdrawn due to AEs have been presented.
All Subjects Population
Posted
Number
Participants
Up to 3.2 years
ID
Title
Description
OG000
Part 1:GSK2816126 50 mg Twice-weekly
Eligible participants received GSK2816126 with a starting dose of 50 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG001
Part 1:GSK2816126 100 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 100 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG002
Part 1:GSK2816126 200 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 200 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG003
Primary
Part 1: Number of Participants With Dose Interruptions
The number of participants who had any dose interruptions have been presented.
All Subjects Population
Posted
Number
Participants
Up to 3.2 years
ID
Title
Description
OG000
Part 1:GSK2816126 50 mg Twice-weekly
Eligible participants received GSK2816126 with a starting dose of 50 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG001
Part 1:GSK2816126 100 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 100 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG002
Part 1:GSK2816126 200 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 200 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG003
Part 1:GSK2816126 400 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 400 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
Primary
Part 1: Number of Participants With Dose Reductions
The number of participants who had any dose reductions have been presented.
All Subjects Population
Posted
Number
Participants
Up to 3.2 years
ID
Title
Description
OG000
Part 1:GSK2816126 50 mg Twice-weekly
Eligible participants received GSK2816126 with a starting dose of 50 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG001
Part 1:GSK2816126 100 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 100 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG002
Part 1:GSK2816126 200 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 200 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG003
Part 1:GSK2816126 400 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 400 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
Primary
Part 1: Number of Participants With Worst Case Change From Baseline in Clinical Chemistry Parameters
Blood samples were collected for evaluation of clinical chemistry parameters including direct bilirubin, chloride, lactate dehydrogenase (LDH), total protein, urea/blood urea nitrogen (BUN) and uric acid. Baseline value was defined as the most recent, non-missing value from a local laboratory prior to the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. The summaries of worst case change from Baseline with respect to normal range have been presented for only those laboratory tests that are not gradable by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The number of participants with decreases to low, changes to normal or no changes from Baseline, and increases to high values have been presented. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
All Subjects Population
Posted
Number
Participants
Baseline and up to 3.2 years
ID
Title
Description
OG000
Part 1:GSK2816126 50 mg Twice-weekly
Eligible participants received GSK2816126 with a starting dose of 50 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG001
Part 1:GSK2816126 100 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 100 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
Primary
Part 1: Number of Participants With Worst Case Change From Baseline in Hematology Parameters
Blood samples were collected for the analysis of hematology parameters including basophils, eosinophils, hematocrit, mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), monocytes, segmented (seg) neutrophils, red blood cell (RBC) count and reticulocytes. Baseline value was defined as the most recent, non-missing value from a local laboratory prior to the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. The summaries of worst case change from Baseline with respect to normal range have been presented for only those laboratory tests that are not gradable by CTCAE version 4.0. The number of participants with decreases to low, changes to normal or no changes from Baseline, and increases to high values have been presented. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
All Subjects Population
Posted
Number
Participants
Baseline and up to 3.2 years
ID
Title
Description
OG000
Part 1:GSK2816126 50 mg Twice-weekly
Eligible participants received GSK2816126 with a starting dose of 50 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG001
Part 1:GSK2816126 100 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 100 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
Primary
Part 1:Number of Participants With Abnormal Values for Vital Signs
Vital sign measurements includes systolic blood pressure (SBP), diastolic blood pressure (DBP), body temperature and heart rate. Vital signs were measured after resting for at least 5 minutes in a semi-supine position. The number of participants with abnormal findings for vital signs have been presented.
All Subjects Population
Posted
Number
Participants
Up to 3.2 years
ID
Title
Description
OG000
Part 1:GSK2816126 50 mg Twice-weekly
Eligible participants received GSK2816126 with a starting dose of 50 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG001
Part 1:GSK2816126 100 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 100 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG002
Part 1:GSK2816126 200 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 200 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG003
Part 1:GSK2816126 400 mg Twice-weekly
Primary
Part 1: Number of Participants With Abnormal Findings for Electrocardiogram (ECG) Parameters
Single measurements of 12-lead ECGs were obtained a semi-recumbent or semi-supine position after at least a 5 minutes rest using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and corrected QT (QTc) intervals. The number of participants with abnormal, abnormal-not clinically significant (NCS), and abnormal-clinically significant (CS) worst case Post Baseline findings have been presented.
All Subjects Population
Posted
Number
Participants
Up to 3.2 years
ID
Title
Description
OG000
Part 1:GSK2816126 50 mg Twice-weekly
Eligible participants received GSK2816126 with a starting dose of 50 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG001
Part 1:GSK2816126 100 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 100 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG002
Part 1:GSK2816126 200 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 200 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
Primary
Part 2: Percentage of Participants Achieving Overall Response Rate
Overall response rate is defined as percentage of participants achieving complete response and partial response per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
All Subjects Population. Data was not collected in Part 2 as no participant was enrolled in Part 2.
Posted
Up to 3.2 years
ID
Title
Description
OG000
Part 2: All Participants
Participants with GCB-DLBCL-mutant and wild type, TFL-mutant and wild type as well as participants with MM were planned to be enrolled in Part 2 of the study. Participants enrolled in Part 2 were planned to receive RP2D .
Units
Counts
Participants
OG000
Secondary
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) Following Single and Repeat Dose Administration of GSK2816126
Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-t) following single (Day 1) and repeat dose (Day 15) administration of GSK2816126. Pharmacokinetic analysis of GSK2816126 in Part 1 was conducted by non-compartmental methods. The analysis was performed on Pharmacokinetic Population which included all participants in the All Subject population for whom a blood sample for pharmacokinetics was analyzed and at least 1 non-missing values was obtained. NA indicates data was not available since geometric coefficient of variation could not be calculated for single participant. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Pharmacokinetic Population
Posted
Geometric Mean
Geometric Coefficient of Variation
Hour*microgram per milliliter
Pre-dose, 0.5, 1, 2, (12, 18 on Day 1 only), 24, and 96 hours post-dose from start of infusion; 0.5, 1, 2, 4, 6 hours from end of infusion on Cycle 1 of Day 1 and Day 15 (Each cycle was of 28 days)
ID
Title
Description
OG000
Part 1:GSK2816126 50 mg Twice-weekly
Eligible participants received GSK2816126 with a starting dose of 50 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG001
Part 1:GSK2816126 100 mg Twice-weekly
Secondary
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK2816126
Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-infinity) following single (Day 1) dose administration of GSK2816126. Pharmacokinetic analysis of GSK2816126 in Part 1 was conducted by non-compartmental methods. NA indicates data was not available since geometric coefficient of variation could not be calculated for single participant. Pharmacokinetic parameter derivation for some participants did not strictly conform to the prescribed acceptance criteria and hence data was not available for those participants.
Pharmacokinetic Population. Only those participants with data available at specific time point were analyzed.
Posted
Geometric Mean
Geometric Coefficient of Variation
Hour*Microgram per milliliter
Pre-dose, 0.5, 1, 2, 12, 18 , 24, and 96 hours post-dose from start of infusion; 0.5, 1, 2, 4, 6 hours from end of infusion on Cycle 1 of Day 1 (Each cycle was of 28 days)
ID
Title
Description
OG000
Part 1:GSK2816126 50 mg Twice-weekly
Eligible participants received GSK2816126 with a starting dose of 50 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG001
Part 1:GSK2816126 100 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 100 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
Secondary
Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK2816126
Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-tau) following repeat (Day 15) dose administration of GSK2816126. Pharmacokinetic analysis of GSK2816126 in Part 1 was conducted by non-compartmental methods. NA indicates data was not available since geometric coefficient of variation could not be calculated for single participant.
Pharmacokinetic Population. Only those participants with data available at specific time point were analyzed.
Posted
Geometric Mean
Geometric Coefficient of Variation
Hour*Microgram per milliliter
Pre-dose, 0.5, 1, 2, 24, and 96 hours post-dose from start of infusion; 0.5, 1, 2, 4, 6 hours from end of infusion on Cycle 1 of Day 15 (Each cycle was of 28 days)
ID
Title
Description
OG000
Part 1:GSK2816126 50 mg Twice-weekly
Eligible participants received GSK2816126 with a starting dose of 50 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG001
Part 1:GSK2816126 100 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 100 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG002
Part 1:GSK2816126 200 mg Twice-weekly
Secondary
Part 1: Trough (Pre-dose) Concentration at the End of Dosing Interval on the Specified Days (Ctau) Following Administration of GSK2816126
Blood samples were collected from participants for pharmacokinetic analysis including Ctau following specified days (Days 8 and 15) administration of GSK2816126. Pharmacokinetic analysis of GSK2816126 in Part 1 was conducted by non-compartmental methods. NA indicates data was not available as data could not be calculated due to limited number of participants at specified data point. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.
Posted
Geometric Mean
Geometric Coefficient of Variation
Microgram per milliliter
Pre-dose from start of infusion till end of infusion on Cycle 1 of Day 8; Pre-dose, 0.5, 1, 2, 24, and 96 hours post-dose from start of infusion; 0.5, 1, 2, 4, 6 hours from end of infusion on Cycle 1 of Day 15 (Each cycle was of 28 days)
ID
Title
Description
OG000
Part 1:GSK2816126 50 mg Twice-weekly
Eligible participants received GSK2816126 with a starting dose of 50 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG001
Part 1:GSK2816126 100 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 100 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
Secondary
Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2816126
Blood samples were collected from participants for pharmacokinetic analysis including Cmax following single (Day 1) and repeat dose (Day 15) administration of GSK2816126. Pharmacokinetic analysis of GSK2816126 in Part 1 was conducted by non-compartmental methods. NA indicates data was not available since geometric coefficient of variation could not be calculated for single participant. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Pharmacokinetic Population
Posted
Geometric Mean
Geometric Coefficient of Variation
Microgram per milliliter
Pre-dose, 0.5, 1, 2, (12, 18 on Day 1 only), 24, and 96 hours post-dose from start of infusion; 0.5, 1, 2, 4, 6 hours from end of infusion on Cycle 1 of Day 1 and Day 15 (Each cycle was of 28 days)
ID
Title
Description
OG000
Part 1:GSK2816126 50 mg Twice-weekly
Eligible participants received GSK2816126 with a starting dose of 50 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG001
Part 1:GSK2816126 100 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 100 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
Secondary
Part 1: Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of GSK2816126
Blood samples were collected from participants for pharmacokinetic analysis including Tmax following single (Day 1) and repeat dose (Day 15) administration of GSK2816126. Tmax is the time to reach Cmax, determined directly from the concentration-time data. Pharmacokinetic analysis of GSK2816126 in Part 1 was conducted by non-compartmental methods. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Pharmacokinetic Population
Posted
Median
Full Range
Hours
Pre-dose, 0.5, 1, 2, (12, 18 on Day 1 only), 24, and 96 hours post-dose from start of infusion; 0.5, 1, 2, 4, 6 hours from end of infusion on Cycle 1 of Day 1 and Day 15 (Each cycle was of 28 days)
ID
Title
Description
OG000
Part 1:GSK2816126 50 mg Twice-weekly
Eligible participants received GSK2816126 with a starting dose of 50 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG001
Part 1:GSK2816126 100 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 100 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG002
Part 1:GSK2816126 200 mg Twice-weekly
Secondary
Part 1: Apparent Terminal Phase Elimination Rate Constant (Lambda z) Following Single and Repeat Dose Administration of GSK2816126
Blood samples were collected from participants for pharmacokinetic analysis including lambda z following single (Day 1) and repeat dose (Day 15) administration of GSK2816126. Pharmacokinetic analysis of GSK2816126 in Part 1 was conducted by non-compartmental methods. Pharmacokinetic parameter derivation for some participants did not strictly conform to the prescribed acceptance criteria and hence data was not available for those participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Pharmacokinetic Population
Posted
Median
Full Range
Hours^-1
Pre-dose, 0.5, 1, 2, (12, 18 on Day 1 only), 24, and 96 hours post-dose from start of infusion; 0.5, 1, 2, 4, 6 hours from end of infusion on Cycle 1 of Day 1 and Day 15 (Each cycle was of 28 days)
ID
Title
Description
OG000
Part 1:GSK2816126 50 mg Twice-weekly
Eligible participants received GSK2816126 with a starting dose of 50 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG001
Part 1:GSK2816126 100 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 100 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
Secondary
Part 1: Apparent Terminal Phase Half-life (T1/2) Following Single and Repeat Dose Administration of GSK2816126
Blood samples were collected from participants for pharmacokinetic analysis including T1/2 following single (Day 1) and repeat dose (Day 15) administration of GSK2816126. Pharmacokinetic analysis of GSK2816126 in Part 1 was conducted by non-compartmental methods. Pharmacokinetic parameter derivation for some participants did not strictly conform to the prescribed acceptance criteria and hence data was not available for those participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Pharmacokinetic Population
Posted
Median
Full Range
Hours
Pre-dose, 0.5, 1, 2, (12, 18 on Day 1 only), 24, and 96 hours post-dose from start of infusion; 0.5, 1, 2, 4, 6 hours from end of infusion on Cycle 1 of Day 1 and Day 15 (Each cycle was of 28 days)
ID
Title
Description
OG000
Part 1:GSK2816126 50 mg Twice-weekly
Eligible participants received GSK2816126 with a starting dose of 50 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG001
Part 1:GSK2816126 100 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 100 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG002
Secondary
Part 1: Accumulation Ratio Following Administration of GSK2816126
Accumulation ratio was determined from the ratio of AUC (0-tau) on Cycle 1 Day 15/AUC (0-tau) on Cycle 1 Day 1 by dose cohort. Only those participants with data available at the specified data points were analyzed. To assess accumulation ratio for a dose level based on ANOVA method, it was required that at least 2 participants had derived PK parameter AUC(0- tau) on both Cycle 1 Day 1 and Cycle 1 Day 15. For dose 100mg, 200mg and 400mg, only 1 participant received treatment. For dose 50mg, 2 participants received treatment but there was one participant whose AUC(0- tau) on Cycle 1 Day 15 could not be derived due to discontinuation of treatment before Day 15. Hence, accumulation ratio could not be calculated for these 4 arms. Accumulation ratio of GSK2816126 was estimated by calculating the ratio of geometric least squares (GLS) means of the AUC between Day 15 and Day 1 for all dose levels and corresponding 90 percent (%) confidence interval (CI) for each ratio.
Pharmacokinetic Population. To assess accumulation ratio by ANOVA, it requires at least 2 participants to derive PK parameter AUC(0- tau) on both Cycle 1 Day 1 and Cycle 1 Day 15 which was not observed for dose 50mg, 100mg, 200mg and 400mg. Hence data could not be calculated for these 4 arms.
Posted
Number
90% Confidence Interval
Ratio of AUC
Pre-dose, 0.5, 1, 2, (12, 18 on Day 1 only), 24, and 96 hours post-dose from start of infusion; 0.5, 1, 2, 4, 6 hours from end of infusion on Cycle 1 of Day 1 and Day 15 (Each cycle was of 28 days)
ID
Title
Description
OG000
Part 1:GSK2816126 800 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 800 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
Secondary
Part 1: Time Invariance Ratio Following Administration of GSK2816126
Ratio of AUC(0-tau) on Day15/Day1 AUC(0-inf) was calculated to assess time invariance. Only those participants with data available at specified data points were analyzed. To assess time invariance based on ANOVA method, it is required that at least 2 participants in a dose level had AUC(0-inf) on Cycle1 Day1 and AUC(0-tau) on Cycle1 Day15. For dose 100mg, 200mg and 400mg, only 1 participant received treatment. For 50mg, 2 participants received treatment but there was one participant whose AUC(0-tau) on Cycle1 Day15 could not be derived due to discontinuation of treatment before Day15, so time invariance could not be calculated. For 1200mg, 4 participants received treatment, however, AUC(0-inf) derivation on Cycle1 Day1 for 3 out of 4 participants did not strictly conform to the prescribed acceptance criteria. Time invariance ratio of GSK2816126 was estimated by calculating ratio of GLS means of AUC between Day15 and Day1 for all dose levels and corresponding 90% CI for each ratio.
Pharmacokinetic Population. To assess time invariance by ANOVA, it requires at least 2 participants to have AUC(0-inf) and AUC(0-tau) on Cycle1 Day15 which was not observed for dose 50mg, 100mg, 200mg, 400mg. For 1200mg, AUC(0-inf) on Cycle1 Day1 for 3 participants did not meet acceptance criteria. Data could not be calculated for these 5 arms.
Posted
Number
90% Confidence Interval
Ratio of AUC
Pre-dose, 0.5, 1, 2, (12, 18 on Day 1 only), 24, and 96 hours post-dose from start of infusion; 0.5, 1, 2, 4, 6 hours from end of infusion on Cycle 1 of Day 1 and Day 15 (Each cycle was of 28 days)
ID
Title
Description
OG000
Part 1:GSK2816126 800 mg Twice-weekly
Secondary
Part 1: Exposure Producing 50 Percent of the Maximum Effect (EC50) of GSK2816126 With Respect to Exposure Markers
The pharmacokinetic/pharmacodynamic relationship between GSK2816126 exposure markers (dose, concentration, Cmax or AUC) was planned to be characterized by linear and/or non-linear mixed effect models. This analysis was planned to be based on Pharmacodynamic Population which consists of participants in the All Subjects population for whom a pharmacodynamics/biomarkers sample was obtained and analyzed. This analysis was planned but not performed as the pharmacodynamic response was not observed and therefore a relationship between pharmacokinetic and pharmacodynamic parameters could not be determined.
Pharmacodynamic Population. Analysis was not performed as pharmacodynamic response was not observed.
Posted
Up to 3.2 years
ID
Title
Description
OG000
Part 1:GSK2816126 50 mg Twice-weekly
Eligible participants received GSK2816126 with a starting dose of 50 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG001
Part 1:GSK2816126 100 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 100 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG002
Part 1:GSK2816126 200 mg Twice-weekly
Secondary
Part 1: Maximum Effect (Emax) of GSK2816126 With Respect to Exposure Markers
The pharmacokinetic/pharmacodynamic relationship between GSK2816126 exposure markers (dose, concentration, Cmax or AUC) was characterized by linear and/or non-linear mixed effect models. This analysis was planned but not performed as the pharmacodynamic response was not observed and therefore a relationship between pharmacokinetic and pharmacodynamic parameters could not be determined.
Pharmacodynamic Population. Analysis was not performed as pharmacodynamic response was not observed.
Posted
Up to 3.2 years
ID
Title
Description
OG000
Part 1:GSK2816126 50 mg Twice-weekly
Eligible participants received GSK2816126 with a starting dose of 50 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG001
Part 1:GSK2816126 100 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 100 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG002
Part 1:GSK2816126 200 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 200 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
Secondary
Part 1: Number of Participants With Overall Change in Tri-methylated Histone H3 Lysine 27 (H3K27me3) Ratios Compared to Baseline
The pre and post-treatment samples for tumor or surrogate tissue/body fluid (e.g. Peripheral blood mononuclear cell [PBMCs], blood, skin or hair) were collected for the analysis of H3K27me3. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline was defined as any visit value minus Baseline value.
Pharmacodynamic Population
Posted
Number
Participants
Baseline and up to 3.2 years
ID
Title
Description
OG000
Part 1:GSK2816126 50 mg Twice-weekly
Eligible participants received GSK2816126 with a starting dose of 50 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG001
Part 1:GSK2816126 100 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 100 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG002
Part 1:GSK2816126 200 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 200 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
Secondary
Part 1: Percentage of Participants With Solid Tumors Achieving Best Overall Response Rate
Overall response rate is defined as percentage of participants achieving complete response and partial response per RECIST version 1.1. Complete Response is the disappearance of all target/non-target lesions. Partial Response is at least a 30 percent decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence. The percentage of participants with solid tumors (including prostate) achieving best overall response rate have been presented. No participants with solid tumors were treated at doses below 800mg (i.e. 50mg, 100mg, 200mg, 400mg). Hence data could not be calculated for these 4 arms.
All Subjects Population.Only those participants with data available at specific time point were analyzed. No participants with solid tumors were treated at doses below 800mg (i.e. 50mg, 100mg, 200mg, 400mg). Hence data could not be calculated for these 4 arms.
Posted
Number
Percentage of participants
Up to 3.2 years
ID
Title
Description
OG000
Part 1:GSK2816126 800 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 800 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG001
Part 1:GSK2816126 1200 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 1200 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
Secondary
Part 1: Percentage of Participants With Lymphoma Achieving Best Overall Response Rate
Overall response rate is defined as percentage of participants achieving complete response and partial response per RECIST version 1.1. Complete Response is the disappearance of all target/non-target lesions. Partial Response is at least a 30 percent decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence. The percentage of participants with lymphoma achieving best overall response rate have been presented.
All Subjects Population
Posted
Number
Percentage of participants
Up to 3.2 years
ID
Title
Description
OG000
Part 1:GSK2816126 50 mg Twice-weekly
Eligible participants received GSK2816126 with a starting dose of 50 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG001
Part 1:GSK2816126 100 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 100 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG002
Part 1:GSK2816126 200 mg Twice-weekly
Secondary
Part 1: Concentration of GSK2816126 and Its Metabolites in Blood
Blood samples were planned to be collected from participants in the pharmacokinetic/pharmacodynamic expansion cohort for analysis of GSK2816126 and its metabolites. Samples were not collected due to early termination of the study; therefore, no analysis could be performed.
Pharmacokinetic Population. Samples were not collected due to early study termination.
Posted
Pre-dose, 0.5, 1, 2, (12, 18 on Day 1 only), 24, and 96 hours post-dose from start of infusion; 0.5, 1, 2, 4, 6 hours from end of infusion on Cycle 1 of Day 1 and Day 15 (Each cycle was of 28 days)
ID
Title
Description
OG000
Part 1: Participants With GCB-DLBCL
At maximum tolerated or recommended phase II dose, participants with GCB-DLBCL were enrolled in Part 1 expansion cohorts and received GSK2816126 twice-weekly, as intravenous solution.
OG001
Part 1: Participants With Solid Tumors
At maximum tolerated or recommended phase II dose, participants with solid tumors were enrolled in Part 1 expansion cohorts and received GSK2816126 twice-weekly, as intravenous solution.
Units
Counts
Participants
Secondary
Part 1: Concentration of GSK2816126 and Its Metabolites in Bile
Bile samples were planned to be collected from participants in the pharmacokinetic/pharmacodynamic expansion cohort for analysis of GSK2816126 and its metabolites via the Entero-Test. Samples were not collected due to early termination of the study; therefore, no analysis could be performed.
Pharmacokinetic Population. Samples were not collected due to early study termination.
Posted
Day 15
ID
Title
Description
OG000
Part 1: Participants With GCB-DLBCL
At maximum tolerated or recommended phase II dose, participants with GCB-DLBCL were enrolled in Part 1 expansion cohorts and received GSK2816126 twice-weekly, as intravenous solution.
OG001
Part 1: Participants With Solid Tumors
At maximum tolerated or recommended phase II dose, participants with solid tumors were enrolled in Part 1 expansion cohorts and received GSK2816126 twice-weekly, as intravenous solution.
Units
Counts
Participants
Secondary
Part 1: Concentration of GSK2816126 and Its Metabolites in Urine
Urine samples were planned to be collected from participants in the pharmacokinetic/pharmacodynamic expansion cohort for analysis of GSK2816126 and its metabolites. Samples were not collected due to early termination of the study; therefore, no analysis could be performed.
Pharmacokinetic Population. Samples were not collected due to early study termination.
Posted
Pre-dose and 0 to 24 hours post-dose on Day 1; 0 to 8 hours post-dose on Day 15
ID
Title
Description
OG000
Part 1: Participants With GCB-DLBCL
At maximum tolerated or recommended phase II dose, participants with GCB-DLBCL were enrolled in Part 1 expansion cohorts and received GSK2816126 twice-weekly, as intravenous solution.
OG001
Part 1: Participants With Solid Tumors
At maximum tolerated or recommended phase II dose, participants with solid tumors were enrolled in Part 1 expansion cohorts and received GSK2816126 twice-weekly, as intravenous solution.
Units
Counts
Participants
Secondary
Part 1:Concentration of GSK2816126 in Urine After Dosing at Steady State
The amount of GSK2816126 excreted in urine after dosing at steady state was determined. The concentration of GSK2816126 in urine was planned to be measured with an investigational bio-analytical method and extrapolated to total amount excreted in urine over time using urine volume. Samples were not collected due to early termination of the study; therefore, no analysis could be performed.
Pharmacokinetic Population Samples were not collected due to early study termination.
Posted
Pre-dose and 0 to 24 hours post-dose on Day 1; 0 to 8 hours post-dose on Day 15
ID
Title
Description
OG000
Part 1:GSK2816126 50 mg Twice-weekly
Eligible participants received GSK2816126 with a starting dose of 50 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG001
Part 1:GSK2816126 100 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 100 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
OG002
Part 1:GSK2816126 200 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 200 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
Secondary
Part 2: Number of Participants With SAEs and Non-SAEs
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/ incapacity, is a congenital anomaly/ birth defect, other situations and is associated with liver injury or impaired liver function. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
All Subjects Population. Data was not collected in Part 2 as no participant was enrolled in Part 2.
Posted
Up to 3.2 years
ID
Title
Description
OG000
Part 2: All Participants
Participants with GCB-DLBCL-mutant and wild type, TFL-mutant and wild type as well as participants with MM were planned to be enrolled in Part 2 of the study. Participants enrolled in Part 2 were planned to receive RP2D .
Units
Counts
Participants
OG000
Secondary
Part 2: Number of Participants With DLTs
An event was considered a DLT if it occurred within first 4 weeks (28 days) of treatment, and met the criteria's for hematologic , non-hematologic, infusion reactions and other toxicities, unless it can be clearly established that the event is unrelated to treatment. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
All Subjects Population. Data was not collected in Part 2 as no participant was enrolled in Part 2.
Posted
Up to 4 weeks
ID
Title
Description
OG000
Part 2: All Participants
Participants with GCB-DLBCL-mutant and wild type, TFL-mutant and wild type as well as participants with MM were planned to be enrolled in Part 2 of the study. Participants enrolled in Part 2 were planned to receive RP2D .
Units
Counts
Participants
OG000
Secondary
Part 2: Number of Participants Withdrawn Due to AEs
A participant was considered to have completed the study if they have completed their end of study visit or if the participant died or was still in follow-up at the time the study was closed or terminated. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
All Subjects Population. Data was not collected in Part 2 as no participant was enrolled in Part 2.
Posted
Up to 3.2 years
ID
Title
Description
OG000
Part 2: All Participants
Participants with GCB-DLBCL-mutant and wild type, TFL-mutant and wild type as well as participants with MM were planned to be enrolled in Part 2 of the study. Participants enrolled in Part 2 were planned to receive RP2D .
Units
Counts
Participants
OG000
Secondary
Part 2: Number of Participants With Dose Interruptions
The number of participants who had any dose interruptions were planned to be analyzed. However, this analysis was not performed for Part 2 as the study was terminated early during Part 1.
All Subjects Population. Data was not collected in Part 2 as no participant was enrolled in Part 2.
Posted
Up to 3.2 years
ID
Title
Description
OG000
Part 2: All Participants
Participants with GCB-DLBCL-mutant and wild type, TFL-mutant and wild type as well as participants with MM were planned to be enrolled in Part 2 of the study. Participants enrolled in Part 2 were planned to receive RP2D .
Units
Counts
Participants
OG000
Secondary
Part 2: Number of Participants With Dose Reductions
The number of participants who had any dose reduction or delay were planned to be analyzed. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
All Subjects Population. Data was not collected in Part 2 as no participant was enrolled in Part 2.
Posted
Up to 3.2 years
ID
Title
Description
OG000
Part 2: All Participants
Participants with GCB-DLBCL-mutant and wild type, TFL-mutant and wild type as well as participants with MM were planned to be enrolled in Part 2 of the study. Participants enrolled in Part 2 were planned to receive RP2D .
Units
Counts
Participants
OG000
Secondary
Part 2: Number of Participants With Worst Case Change From Baseline in Clinical Chemistry Parameters
Blood samples were planned to be collected for evaluation of clinical chemistry parameters including direct bilirubin, chloride, LDH, total protein, urea/BUN and uric acid. Baseline value was defined as the most recent, non-missing value from a local laboratory prior to the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
All Subjects Population. Data was not collected in Part 2 as no participant was enrolled in Part 2.
Posted
Baseline and up to 3.2 years
ID
Title
Description
OG000
Part 2: All Participants
Participants with GCB-DLBCL-mutant and wild type, TFL-mutant and wild type as well as participants with MM were planned to be enrolled in Part 2 of the study. Participants enrolled in Part 2 were planned to receive RP2D .
Units
Counts
Participants
OG000
Secondary
Part 2: Number of Participants With Worst Case Changes From Baseline in Hematology Parameters
Blood samples were planned to be collected for the analysis of hematology parameters including basophils, eosinophils, hematocrit, MCHC, MCH, MCV, monocytes, seg neutrophils, RBC count and reticulocytes. Baseline value was defined as the most recent, non-missing value from a local laboratory prior to the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
All Subjects Population. Data was not collected in Part 2 as no participant was enrolled in Part 2.
Posted
Baseline and up to 3.2 years
ID
Title
Description
OG000
Part 2: All Participants
Participants with GCB-DLBCL-mutant and wild type, TFL-mutant and wild type as well as participants with MM were planned to be enrolled in Part 2 of the study. Participants enrolled in Part 2 were planned to receive RP2D .
Units
Counts
Participants
OG000
Secondary
Part 2: Number of Participants With Abnormal Values for Vital Signs
Vital sign measurements includes SBP, DBP, body temperature and heart rate. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
All Subjects Population. Data was not collected in Part 2 as no participant was enrolled in Part 2.
Posted
Up to 3.2 years
ID
Title
Description
OG000
Part 2: All Participants
Participants with GCB-DLBCL-mutant and wild type, TFL-mutant and wild type as well as participants with MM were planned to be enrolled in Part 2 of the study. Participants enrolled in Part 2 were planned to receive RP2D .
Units
Counts
Participants
OG000
Secondary
Part 2: Number of Participants With Abnormal Findings for ECG Parameters
Single measurements of 12-lead ECGs were planned to be obtained a semi-recumbent or semi-supine position after at least a 5 minutes rest using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QTc intervals. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
All Subjects Population. Data was not collected in Part 2 as no participant was enrolled in Part 2.
Posted
Up to 3.2 years
ID
Title
Description
OG000
Part 2: All Participants
Participants with GCB-DLBCL-mutant and wild type, TFL-mutant and wild type as well as participants with MM were planned to be enrolled in Part 2 of the study. Participants enrolled in Part 2 were planned to receive RP2D .
Units
Counts
Participants
OG000
Secondary
Part 2: Clearance Following Administration of GSK2816126
Blood samples were planned to be collected at Pre-dose, single draw between 0.5 and 1.9 hours from start of infusion, single draw between 3-6 hours following end of infusion on Day 1 and Day 11; Pre-dose on Day 4; Day 8, Day 11; Pre-dose on Day 15 for Cycle 1 and Cycles 2, 4, 6 and 12 pre-dose and within 5 minutes prior to end of infusion on Day 4 for population pharmacokinetic analysis of GSK2816126 including clearance. Each cycle was of 28 days. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Pharmacokinetic Population. Data was not collected in Part2 as no participant was enrolled in Part2.
Posted
Up to 3.2 years
ID
Title
Description
OG000
Part 2: All Participants
Participants with GCB-DLBCL-mutant and wild type, TFL-mutant and wild type as well as participants with MM were planned to be enrolled in Part 2 of the study. Participants enrolled in Part 2 were planned to receive RP2D .
Units
Counts
Participants
OG000
Secondary
Part 2: Volume of Distribution Following Administration of GSK2816126
Blood samples were planned to be collected on Pre-dose, single draw between 0.5 and 1.9 hours from start of infusion, single draw between 3-6 hours following end of infusion on Day 1 and Day 11; Pre-dose on Day 4; Day 8,Day 11; Pre-dose on Day 15 for Cycle 1 and Cycle 2, 4, 6 and 12 pre-dose and within 5 minutes prior to end of infusion on Day 4 for population pharmacokinetic analysis of GSK2816126 including clearance. Each cycle was of 28 days. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Pharmacokinetic Population. Data was not collected in Part2 as no participant was enrolled in Part2.
Posted
Up to 3.2 years
ID
Title
Description
OG000
Part 2: All Participants
Participants with GCB-DLBCL-mutant and wild type, TFL-mutant and wild type as well as participants with MM were planned to be enrolled in Part 2 of the study. Participants enrolled in Part 2 were planned to receive RP2D .
Units
Counts
Participants
OG000
Secondary
Part 2:EC50 of GSK2816126 With Respect to Exposure Markers
The pharmacokinetic/pharmacodynamic relationship between GSK2816126 exposure markers (dose, concentration, Cmax or AUC) was planned to be characterized by linear and/or non-linear mixed effect models. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Pharmacodynamic Population. Data was not collected in Part2 as no participant was enrolled in Part2.
Posted
Up to 3.2 years
ID
Title
Description
OG000
Part 2: All Participants
Participants with GCB-DLBCL-mutant and wild type, TFL-mutant and wild type as well as participants with MM were planned to be enrolled in Part 2 of the study. Participants enrolled in Part 2 were planned to receive RP2D .
Units
Counts
Participants
OG000
Secondary
Part 2:Emax of GSK2816126 With Respect to Exposure Markers
The pharmacokinetic/pharmacodynamic relationship between GSK2816126 exposure markers (dose, concentration, Cmax or AUC) was planned to be characterized by linear and/or non-linear mixed effect models. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Pharmacodynamic Population. Data was not collected in Part2 as no participant was enrolled in Part2.
Posted
Up to 3.2 years
ID
Title
Description
OG000
Part 2: All Participants
Participants with GCB-DLBCL-mutant and wild type, TFL-mutant and wild type as well as participants with MM were planned to be enrolled in Part 2 of the study. Participants enrolled in Part 2 were planned to receive RP2D .
Units
Counts
Participants
OG000
Secondary
Part 2: Number of Participants With Change in H3K27me3 Ratios Compared to Baseline
The pre and post-treatment samples for tumor or surrogate tissue/body fluid (e.g. PBMCs, blood, skin or hair) were planned to be collected for the analysis of H3K27me3. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline was defined as any visit value minus Baseline value. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Pharmacodynamic Population. Data was not collected in Part2 as no participant was enrolled in Part2.
Posted
Baseline and up to 3.2 years
ID
Title
Description
OG000
Part 2: All Participants
Participants with GCB-DLBCL-mutant and wild type, TFL-mutant and wild type as well as participants with MM were planned to be enrolled in Part 2 of the study. Participants enrolled in Part 2 were planned to receive RP2D .
Units
Counts
Participants
OG000
Secondary
Part 2: Concentration of GSK2816126 and Its Metabolites in Blood
Blood samples were planned to be collected from participants in the pharmacokinetic/pharmacodynamic expansion cohort for analysis of GSK2816126 and its metabolites. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Pharmacokinetic Population. Data was not collected in Part2 as no participant was enrolled in Part2.
Posted
Pre-dose, single draw between 0.5 and 1.9 hours from start of infusion, single draw between 3-6 hours following end of infusion on Day 1; Pre-dose on Day 15 for Cycle 1 and Cycles 2, 4, 6 and 12 (Each cycle was of 28 days)
ID
Title
Description
OG000
Part 2: All Participants
Participants with GCB-DLBCL-mutant and wild type, TFL-mutant and wild type as well as participants with MM were planned to be enrolled in Part 2 of the study. Participants enrolled in Part 2 were planned to receive RP2D .
Units
Counts
Participants
OG000
Secondary
Part 2: Concentration of GSK2816126 and Its Metabolites in Bile
Bile samples were planned to be collected from participants in the pharmacokinetic/pharmacodynamic expansion cohort for analysis of GSK2816126 and its metabolites via the Entero-Test. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Pharmacokinetic Population. Data was not collected in Part2 as no participant was enrolled in Part2.
Posted
Day 15
ID
Title
Description
OG000
Part 2: All Participants
Participants with GCB-DLBCL-mutant and wild type, TFL-mutant and wild type as well as participants with MM were planned to be enrolled in Part 2 of the study. Participants enrolled in Part 2 were planned to receive RP2D .
Units
Counts
Participants
OG000
Secondary
Part 2: Concentration of GSK2816126 and Its Metabolites in Urine
Urine samples were planned to be collected from participants in the pharmacokinetic/pharmacodynamic expansion cohort for analysis of GSK2816126 and its metabolites. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Pharmacokinetic Population. Data was not collected in Part2 as no participant was enrolled in Part2.
Posted
Pre-dose and 0 to 24 hours post-dose on Day 1; 0 to 8 hours post-dose on Day 15
ID
Title
Description
OG000
Part 2: All Participants
Participants with GCB-DLBCL-mutant and wild type, TFL-mutant and wild type as well as participants with MM were planned to be enrolled in Part 2 of the study. Participants enrolled in Part 2 were planned to receive RP2D .
Units
Counts
Participants
OG000
Secondary
Part 2:Concentration of GSK2816126 in Urine After Dosing at Steady State
The amount of GSK2816126 excreted in urine after dosing at steady state was planned to be determined. The concentration of GSK2816126 in urine was planned to be measured with an investigational bio-analytical method and extrapolated to total amount excreted in urine over time using urine volume. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Pharmacokinetic Population. Data was not collected in Part2 as no participant was enrolled in Part2.
Posted
Pre-dose and 0 to 24 hours post-dose on Day 1; 0 to 8 hours post-dose on Day 15
ID
Title
Description
OG000
Part 2: All Participants
Participants with GCB-DLBCL-mutant and wild type, TFL-mutant and wild type as well as participants with MM were planned to be enrolled in Part 2 of the study. Participants enrolled in Part 2 were planned to receive RP2D .
Units
Counts
Participants
OG000
Secondary
Part 2: Change in 4-beta-hydroxy Cholesterol to Cholesterol Ratio From Baseline Following Repeat Dosing of GSK2816126
Plasma analysis for 4-beta-hydroxycholesterol and cholesterol was planned to be conducted. Baseline value was defined as the most recent, non-missing value from a local laboratory prior to the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Pharmacodynamic Population. Data was not collected in Part2 as no participant was enrolled in Part2.
Posted
Baseline and up to 21 days
ID
Title
Description
OG000
Part 2: All Participants
Participants with GCB-DLBCL-mutant and wild type, TFL-mutant and wild type as well as participants with MM were planned to be enrolled in Part 2 of the study. Participants enrolled in Part 2 were planned to receive RP2D .
Units
Counts
Participants
OG000
Secondary
Part 2: Duration of Response
Duration of response for participants is defined as the time from the first documented evidence of a PR or CR until the first documented sign of disease progression or death due to any cause. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
All Subjects Population. Data was not collected in Part 2 as no participant was enrolled in Part 2.
Posted
Up to 3.2 years
ID
Title
Description
OG000
Part 2: All Participants
Participants with GCB-DLBCL-mutant and wild type, TFL-mutant and wild type as well as participants with MM were planned to be enrolled in Part 2 of the study. Participants enrolled in Part 2 were planned to receive RP2D .
Units
Counts
Participants
OG000
Secondary
Part 2: Number of Participants With Progression Free Survival
PFS is defined as the interval between the first dose of study medication and the earliest date of disease progression or death due to any cause. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
All Subjects Population. Data was not collected in Part 2 as no participant was enrolled in Part 2.
Posted
Up to 3.2 years
ID
Title
Description
OG000
Part 2: All Participants
Participants with GCB-DLBCL-mutant and wild type, TFL-mutant and wild type as well as participants with MM were planned to be enrolled in Part 2 of the study. Participants enrolled in Part 2 were planned to receive RP2D .
Units
Counts
Participants
OG000
Time Frame
Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected in Part 1 from the start of the study treatment up to 3.2 years.
Description
SAEs and Non-SAEs were collected in Part A from All Subjects Population which included all participants who receive at least one dose of study treatment. Data were not collected in Part 2 as no participant was enrolled in Part 2.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Part 1:GSK2816126 50 mg Twice-weekly
Eligible participants received GSK2816126 with a starting dose of 50 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
1
2
1
2
2
2
EG001
Part 1:GSK2816126 100 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 100 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
0
1
0
1
1
1
EG002
Part 1:GSK2816126 200 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 200 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
0
1
0
1
1
1
EG003
Part 1:GSK2816126 400 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 400 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
0
1
0
1
1
1
EG004
Part 1:GSK2816126 800 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 800 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
0
3
1
3
3
3
EG005
Part 1:GSK2816126 1200 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 1200 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
1
4
2
4
4
4
EG006
Part 1:GSK2816126 1800 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 1800 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
2
10
1
10
10
10
EG007
Part 1:GSK2816126 2400 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 2400 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
0
12
5
12
12
12
EG008
Part 1:GSK2816126 3000 mg Twice-weekly
Eligible participants received GSK2816126 with a dose of 3000 mg twice-weekly, as an intravenous solution for 28 days (3 weeks on/1 week off).
1
7
3
7
7
7
EG009
Part 2: All Participants
Participants with GCB-DLBCL-mutant and wild type, TFL-mutant and wild type as well as participants with MM were planned to be enrolled in Part 2 of the study. Participants enrolled in Part 2 were planned to receive RP2D .
0
0
0
0
0
0
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Pyrexia
General disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG0030 events0 affected1 at risk
EG0040 events0 affected3 at risk
EG0051 events1 affected4 at risk
EG0060 events0 affected10 at risk
EG0071 events1 affected12 at risk
EG0081 events1 affected7 at risk
EG0090 events0 affected0 at risk
Respiratory tract infection
Infections and infestations
MedDRA20.1
Systematic Assessment
EG0001 events1 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Bronchitis
Infections and infestations
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Campylobacter infection
Infections and infestations
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Enterocolitis
Gastrointestinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Haemoptysis
Respiratory, thoracic and mediastinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Intestinal obstruction
Gastrointestinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Pneumonia
Infections and infestations
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Skin bacterial infection
Infections and infestations
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Tumour pain
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Fatigue
General disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0011 events1 affected1 at risk
EG0021 events1 affected1 at risk
EG0031 events1 affected1 at risk
EG0042 events2 affected3 at risk
EG0052 events2 affected4 at risk
EG0066 events6 affected10 at risk
EG0077 events7 affected12 at risk
EG0082 events2 affected7 at risk
EG0090 events0 affected0 at risk
Nausea
Gastrointestinal disorders
MedDRA20.1
Systematic Assessment
EG0001 events1 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Anaemia
Blood and lymphatic system disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA20.1
Systematic Assessment
EG0001 events1 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA20.1
Systematic Assessment
EG0001 events1 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Infusion related reaction
Injury, poisoning and procedural complications
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA20.1
Systematic Assessment
EG0001 events1 affected2 at risk
EG0010 events0 affected1 at risk
EG0021 events1 affected1 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA20.1
Systematic Assessment
EG0001 events1 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Paraesthesia oral
Gastrointestinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Pyrexia
General disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0021 events1 affected1 at risk
EG003
Blood alkaline phosphatase increased
Investigations
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA20.1
Systematic Assessment
EG0001 events1 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Hypomagnesaemia
Metabolism and nutrition disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Oedema peripheral
General disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0011 events1 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Tumour pain
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA20.1
Systematic Assessment
EG0001 events1 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Blood creatinine increased
Investigations
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA20.1
Systematic Assessment
EG0001 events1 affected2 at risk
EG0011 events1 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Lymphopenia
Blood and lymphatic system disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Neuropathy peripheral
Nervous system disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Rash maculo-papular
Skin and subcutaneous tissue disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Abdominal discomfort
Gastrointestinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Asthenia
General disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Chest discomfort
General disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Chills
General disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Depression
Psychiatric disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Dysphonia
Respiratory, thoracic and mediastinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Electrocardiogram QT prolonged
Investigations
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0011 events1 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Headache
Nervous system disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Hot flush
Vascular disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Hypoaesthesia oral
Gastrointestinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Hypotension
Vascular disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0011 events1 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Influenza like illness
General disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Lower respiratory tract infection
Infections and infestations
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0011 events1 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Medical device site reaction
General disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0011 events1 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0021 events1 affected1 at risk
EG003
Night sweats
Skin and subcutaneous tissue disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Tachycardia
Cardiac disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA20.1
Systematic Assessment
EG0001 events1 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Urticaria
Skin and subcutaneous tissue disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Abdominal tenderness
Gastrointestinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Anal paraesthesia
Gastrointestinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Application site pruritus
General disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0011 events1 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Atrial fibrillation
Cardiac disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Blood creatinine decreased
Investigations
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Blood uric acid decreased
Investigations
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Bronchitis
Infections and infestations
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Chest pain
General disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0011 events1 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Complication associated with device
General disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Conjunctival hyperaemia
Eye disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0011 events1 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Deep vein thrombosis
Vascular disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Dizziness
Nervous system disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Drug hypersensitivity
Immune system disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Dysaesthesia
Nervous system disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0021 events1 affected1 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Dysphagia
Gastrointestinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Ear disorder
Ear and labyrinth disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0011 events1 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Electrocardiogram T wave abnormal
Investigations
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0011 events1 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Erythema
Skin and subcutaneous tissue disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0021 events1 affected1 at risk
EG003
Face oedema
General disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Febrile neutropenia
Blood and lymphatic system disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Feeling abnormal
General disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Feeling hot
General disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Feeling of body temperature change
General disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Flushing
Vascular disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Furuncle
Infections and infestations
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Haemoptysis
Respiratory, thoracic and mediastinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Hallucination, auditory
Psychiatric disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Hepatocellular injury
Hepatobiliary disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Hydronephrosis
Renal and urinary disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Hyperbilirubinaemia
Hepatobiliary disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Hypercalcaemia
Metabolism and nutrition disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Hyperhidrosis
Skin and subcutaneous tissue disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Hypertension
Vascular disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Hyperuricaemia
Metabolism and nutrition disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Hypoalbuminaemia
Metabolism and nutrition disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Lymphocyte count decreased
Investigations
MedDRA20.1
Systematic Assessment
EG0001 events1 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Lymphoedema
Vascular disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Malaise
General disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Mucosal inflammation
General disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Muscle contractions involuntary
Nervous system disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Muscle twitching
Musculoskeletal and connective tissue disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Nasal congestion
Respiratory, thoracic and mediastinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Neuralgia
Nervous system disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Neutrophil count decreased
Investigations
MedDRA20.1
Systematic Assessment
EG0001 events1 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Oral candidiasis
Infections and infestations
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Oral dysaesthesia
Gastrointestinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Palmar erythema
Skin and subcutaneous tissue disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Pneumonitis
Respiratory, thoracic and mediastinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Pollakiuria
Renal and urinary disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Procedural pain
Injury, poisoning and procedural complications
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Productive cough
Respiratory, thoracic and mediastinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0011 events1 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0011 events1 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Rash macular
Skin and subcutaneous tissue disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Rash papular
Skin and subcutaneous tissue disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Rectal tenesmus
Gastrointestinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Rhinitis
Infections and infestations
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Rhinorrhoea
Respiratory, thoracic and mediastinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Sinus congestion
Respiratory, thoracic and mediastinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0011 events1 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Skin abrasion
Injury, poisoning and procedural complications
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0011 events1 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Skin infection
Infections and infestations
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Skin necrosis
Skin and subcutaneous tissue disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Stomatitis
Gastrointestinal disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Suprapubic pain
General disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Telangiectasia
Skin and subcutaneous tissue disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0021 events1 affected1 at risk
EG003
Testicular pain
Reproductive system and breast disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Tooth abscess
Infections and infestations
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0011 events1 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Urine output decreased
Investigations
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Viral infection
Infections and infestations
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Vision blurred
Eye disorders
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Vitamin D decreased
Investigations
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Weight decreased
Investigations
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
White blood cell count decreased
Investigations
MedDRA20.1
Systematic Assessment
EG0002 events1 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
Wound infection
Infections and infestations
MedDRA20.1
Systematic Assessment
EG0000 events0 affected2 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected1 at risk
EG003
This study was terminated prior to the completion of Part 1 due to an unfavorable benefit risk profile. Part 2 was never initiated and no participants were enrolled. Participants time on treatment was for a maximum 210 days and a median of 56 days.
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.