Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Heart and Blood Diseases

Rare Diseases

Lymphoma, Large B-Cell, Diffuse

Lymphoma

Multiple Myeloma

Neoplasms, Plasma Cell

Lymphoma, Follicular

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Lymphosarcoma

Follicular Lymphoma

Pharmaceutical Solutions

All Drugs and Chemicals

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

GSK2816126 will be supplied as a solution containing 15 milligram per milliliter (mg/mL) GSK2816126 in water for injection.

GSK2816126

GSK Clinical Trials

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.

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.

This will be an open-label study. Hence, there will be no masking.

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

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

IPD for this study will be made available via the Clinical Study Data Request site.

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.

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.

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.

The number of participants who had any dose interruptions have been presented.

The number of participants who had any dose reductions have been presented.

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).

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).

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.

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.

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.

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).

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.

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.

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).

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).

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).

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).

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

GlaxoSmithKline

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.

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).

Part 1:GSK2816126 50 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).

Part 1:GSK2816126 100 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).

Part 1:GSK2816126 200 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).

Part 1:GSK2816126 400 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).

Part 1:GSK2816126 800 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).

Part 1:GSK2816126 1200 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).

Part 1:GSK2816126 1800 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).

Part 1:GSK2816126 2400 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).

Part 1:GSK2816126 3000 mg Twice-weekly

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 .

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) .

Total

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

Data was not collected in Part 2 of the study as no participant was enrolled in Part 2.

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.

GSK Response Center

Any Non-SAE

Any SAE

Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs)

Part 1: Number of Participants With Dose Limiting Toxicities (DLT)

Part 1: Number of Participants Withdrawn Due to AEs

Part 1: Number of Participants With Dose Interruptions

Part 1: Number of Participants With Dose Reductions

Direct Bilirubin; To Low; n=1,1,1,1,3,4,8,12,7

Direct Bilirubin; To Normal; n=1,1,1,1,3,4,8,12,7

Direct Bilirubin; To High; n=1,1,1,1,3,4,8,12,7

Chloride; To Low;n=2,1,1,1,3,4,10,12,7

Chloride; To Normal; n=2,1,1,1,3,4,10,12,7

Chloride; To High; n=2,1,1,1,3,4,10,12,7

LDH; To Low; n=2,1,1,1,3,4,10,12,7

LDH; To Normal; n=2,1,1,1,3,4,10,12,7

LDH; To High; n=2,1,1,1,3,4,10,12,7

Total Protein; To Low n=2,1,1,1,3,4,10,12,7

Total Protein; To Normal; n=2,1,1,1,3,4,10,12,7

Total Protein; To High; n=2,1,1,1,3,4,10,12,7

Urea/BUN; To Low; n=2,1,1,1,3,4,10,12,7

Urea/BUN; To Normal; n=2,1,1,1,3,4,10,12,7

Urea/BUN; To High; n=2,1,1,1,3,4,10,12,7

Uric acid; To Low; n=2,1,1,1,3,4,10,12,7

Uric acid; To Normal; n=2,1,1,1,3,4,10,12,7

Uric acid; To High; n=2,1,1,1,3,4,10,12,7

Part 1: Number of Participants With Worst Case Change From Baseline in Clinical Chemistry Parameters

Basophils; To Low; n=2,1,1,1,3,4,10,12,7

Basophils; To Normal; n=2,1,1,1,3,4,10,12,7

Basophils; To High; n=2,1,1,1,3,4,10,12,7

Eosinophils; To Low; n=2,1,1,1,3,4,10,12,7

Eosinophils; To Normal; n=2,1,1,1,3,4,10,12,7

Eosinophils; To High; n=2,1,1,1,3,4,10,12,7

Hematocrit; To Low; n=2,1,1,1,3,4,10,12,7

Hematocrit; To Normal; n=2,1,1,1,3,4,10,12,7

Hematocrit; To High; n=2,1,1,1,3,4,10,12,7

MCHC; To Low; n=2,1,1,1,3,4,10,12,7

MCHC; To Normal; n=2,1,1,1,3,4,10,12,7

MCHC; To High; n=2,1,1,1,3,4,10,12,7

MCH; To Low; n=2,1,1,1,3,4,10,12,7

MCH; To Normal; n=2,1,1,1,3,4,10,12,7

MCH; To High; n=2,1,1,1,3,4,10,12,7

MCV; To Low; n=2,1,1,1,3,4,10,12,7

MCV; To Normal; n=2,1,1,1,3,4,10,12,7

MCV; To High; n=2,1,1,1,3,4,10,12,7

Monocytes; To Low; n=2,1,1,1,3,4,10,12,7

Monocytes; To Normal; n=2,1,1,1,3,4,10,12,7

Monocytes; To High; n=2,1,1,1,3,4,10,12,7

Seg Neutrophils; To Low; n= 0,0,0,0,0,0,0,0,1

Seg Neutrophils; To Normal; n= 0,0,0,0,0,0,0,0,1

Seg Neutrophils; To High; n= n= 0,0,0,0,0,0,0,0,1

RBC count; To Low; n=2,1,1,1,3,4,10,12,7

RBC count; To Normal; n=2,1,1,1,3,4,10,12,7

RBC count; To High; n=2,1,1,1,3,4,10,12,7

Reticulocytes; ; To Low; n=2,1,1,1,3,4,10,12,7

Reticulocytes; To Normal; n=2,1,1,1,3,4,10,12,7

Reticulocytes; To High; n=2,1,1,1,3,4,10,12,7

Part 1: Number of Participants With Worst Case Change From Baseline in Hematology Parameters

Heart rate

Body temperature

Part 1:Number of Participants With Abnormal Values for Vital Signs

Abnormal; NCS

Abnormal; CS

Abnormal

Part 1: Number of Participants With Abnormal Findings for Electrocardiogram (ECG) Parameters

All Subjects Population. Data was not collected in Part 2 as no participant was enrolled in Part 2.

Part 2: Percentage of Participants Achieving Overall Response Rate

Day 1; n=2,1,1,1,3,4,10,12,7

Day 15; n=1,1,1,1,3,4,9,11,4

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

Pharmacokinetic Population. Only those participants with data available at specific time point were analyzed.

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

Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK2816126

Day 8; n=2,1,1,1,3,4,9,11,6

Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed.

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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