Leukaemia, Myelocytic, Acute
Conditions
Keywords
Oncology, LSD1, GSK2879552, Acute myeloid leukemia
Brief summary
This study is a phase I, open-label study to determine recommended phase 2 dose (RP2D) and regimen for the orally administered lysine specific demethylase 1 (LSD1) inhibitor GSK2879552, alone or in combination with All-Trans Retinoic Acid (ATRA). The recommended dose and regimen will be selected based on the safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles observed after the treatment of subjects with relapsed/refractory AML. The study consists of two parts. Part 1 will identify the maximum tolerated dose (MTD) and/or RP2D using a dose-escalation procedure. Dose escalations will be guided by the Neuenschwander-continual reassessment method (N-CRM). PK/PD expansion cohorts will also be included in Part 1 to characterize the range of biologically effective doses by assessing PD markers and obtain additional PK data. Part 2 will explore further the safety, tolerability, and clinical activity of GSK2879552, alone or in combination with ATRA, at the RP2D in subjects with AML.
Interventions
DRUGGSK2879552
GSK2879552 capsules contain 0.25 mg, 0.5 mg, 2 mg or 5 mg of GSK2879552 as parent. The initial dosing regimen will be continuous oral daily dosing.
DRUGATRA
ATRA (Tretinoin) will be supplied as a 10 mg capsule for oral administration. The initial dosing regimen will be continuous oral twice daily dosing
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects \>=18 years of age and provided signed written informed consent. * Subjects must have relapsed/refractory AML by world health organization (WHO) classification for which no standard therapies are available or anticipated to result in a durable remission. French- American- British system (FAB) subtype M3 will be excluded. * Subjects \>= 60 years of age with AML who are not candidates for or have refused standard chemotherapy. * Subjects who have previously received an autologous stem cell transplant are allowed if a minimum of 3 months has elapsed from the time of transplant and the subject has recovered from transplant-associated toxicities prior to the first dose of GSK2879552. * Subjects with a history of allogeneic stem cell transplant are eligible for study participation provided the following eligibility criteria are met: transplant was \>60 days prior to study enrolment; subject has not taken immunosuppressive medications for at least 1 month; no signs or symptoms of graft versus host disease other than Grade 1 skin involvement; no active infection. * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. * Subjects must be stable and, in the opinion of the investigator, be expected to complete 4 week treatment period. * Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels. * All prior treatment-related toxicities must be National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.0 \<=Grade 1 at the time of enrollment (except for alopecia). * Adequate baseline organ function. * Women of childbearing potential must have a negative serum pregnancy test within 7 days of first dose of study treatment and agree to use effective contraception, during the study and for 7 days (GSK2879552 mono therapy) or 30 days (combination with ATRA), following the last dose of study treatment. * Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception from the administration of the first dose of study treatment until 3 months after the last dose of study treatment to allow for clearance of any altered sperm.
Exclusion criteria
* Active human immunodeficiency virus (HIV), Hepatitis B Virus (HBV) or hepatitis C virus (HCV) infections at the time of screening. Subjects with laboratory evidence of HCV clearance may be enrolled. * History of or concurrent malignancy of solid tumours, except: subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. Subjects with second malignancies that are indolent or definitively treated may be enrolled even if less than 5 years have elapsed since treatment. Consult GlaxoSmithKline (GSK) Medical Monitor if unsure whether second malignancies meet requirements specified above. * Currently receiving cancer therapy. Hydroxyurea will be allowed. * Received major surgery, radiotherapy, or immunotherapy within 4 weeks of GSK2879552 administration. * Prior treatment with temozolomide, dacarbazine or procarbazine * Prior treatment with poly ADP ribose polymerase (PARP) inhibitors (eg., olaparib, ABT-888) * Baseline Montreal Cognitive Assessment (MOCA) score of 22 or lower * Evidence of severe or uncontrolled systemic diseases. Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the Investigator * Current active liver or biliary disease. * Patients at risk of non-AML related major bleeding (e.g. recent gastrointestinal \[GI\] hemorrhage or neurosurgery). * Symptomatic or untreated central nervous system (CNS) leukemia. Subjects are permitted to enroll if previously treated for CNS disease, free of symptoms at the time of screening, and have not required intrathecal chemotherapy at least 1 month prior to study Day 1. * Cardiac abnormalities * Administration of an investigational drug within 14 days or 5 half-lives, whichever is shorter with a minimum of 14 days preceding the first dose of study treatment(s) in this study. * Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GSK2879552 or LSD1 inhibitors that contraindicates their participation. * Lactating female. * Consumption of Seville oranges, grapefruit, grapefruit hybrids, grapefruit juice, pommelos, or exotic citrus fruits, from 1 day prior to the first dose of study treatment(s) until the last dose of study drug. * Current use of a prohibited medication including anticoagulants or platelet inhibitors or expected to require any of these medications during treatment with the investigational drug. * Previous treatment with GSK2879552 For ATRA Combination arm ONLY * Known hypersensitivity to ATRA, parabens (preservatives in the gelatin capsule) or other retinoids. * ATRA capsule contains sorbitol. Subjects with rare hereditary problems of fructose intolerance are excluded. * History of seizure within 12 months or brain tumor (primary) * History of taking mega-dose vitamin A (\>25,000 USP U/day) within 3 months from the dosing start.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Median of 4 weeks of drug exposure | An AE is any untoward medical occurrence in a 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, is a congenital anomaly/ birth defect, other situations and is associated with liver injury or impaired liver function. |
| Part 1: Number of Participants With Dose Limiting Toxicities (DLT) | Median of 4 weeks of drug exposure | An event was considered a DLT if it occursed within the first 28 days of treatment, and meets one of the following criteria unless it can be clearly established that the event was unrelated to treatment: hematologic DLT included myelosuppression, Grade \>=3 non-hematologic toxicity that is considered clinically significant and lasts \>72 hours, Grade 2 toxicity that in the judgment of the investigator and GSK Medical Monitor is dose-limiting and treatment delay of \>=42 days due to unresolved toxicity. |
| Part 1: Number of Participants With AE Leading to Dose Reductions or Delays | Median of 4 weeks of drug exposure | The number of participants who had any dose reduction or delay have been presented. |
| Part 1: Number of Participants With Withdrawals Due to Toxicities | Median of 4 weeks of drug exposure | Participants were monitored from start of the study till the development of toxicity. The data for number of participants withdrawn due to toxicities has been presented. |
| Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Median of 4 weeks of drug exposure | Blood samples were collected to assess clinical chemistry parameters like urea/blood urea nitrogen (BUN), calcium, potassium, aspartate aminotransferase (AST), total bilirubin, direct bilirubin, creatinine, chloride, alanine aminotransferase (ALT), uric acid, glucose, total carbon dioxide (CO2), gamma glutamyl transferase (GGT), albumin, sodium, alkaline phosphatase, total protein, phosphate, lactate dehydrogenase (LDH). Laboratory values were as per local labs per site with own normal ranges. Values above range were reported as high and values below range as low. Data for worst case post Baseline is reported. |
| Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Median of 4 weeks of drug exposure | Blood samples were collected for analysis of clinical chemistry parameters based on common terminology criteria for adverse events (CTCAE) version 4.0, where Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life threatening consequences. Data for any increase in grade of worst-case on-therapy has been provided. |
| Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Median of 4 weeks of drug exposure | Blood samples were collected to assess hematology parameters like mean corpuscle hemoglobin concentration (MCHC), mean corpuscle hemoglobin (MCH), mean corpuscle volume (MCV) mean platelet volume (MPV), basophils, eosinophils, hematocrit, hemoglobin, lymphocytes, monocytes, platelet count, Red blood cell (RBC) count, reticulocytes, White Blood Cell (WBC) count. Laboratory values were as per local labs per site with own normal ranges. Values above range were reported as high and values below range as low. Data for worst post Baseline were reported. NA indicates that data were not available as standard deviation could not be calculated for a single participant. |
| Number of Participants With Hematology Toxicity Grade Changes From Baseline | Median of 4 weeks of drug exposure | Blood samples were collected for analysis of hematology parameters based on common terminology criteria for adverse events (CTCAE) version 4.0, where Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life threatening consequences. Data for any grade increase worst-case on-therapy has been provided. |
| Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Median of 4 weeks of drug exposure | SBP and DBP were measured after resting for 5 minutes in semi-supine position. Vital signs were graded according to Common Toxicity Criteria for Adverse Events (CTCAE) version 4. An increase is defined as an increase in CTCAE grade relative to Baseline grade. For SBP Grade 0 (\<120 millimeters of mercury \[mmHg\]), Grade 1 (120-139 mmHg), Grade 2 (140-159 mmHg), Grade 3 (\>=160 mmHg). For DBP Grade 0 (\<80 mmHg), Grade 1 (80-89 mmHg), Grade 2 (90-99 mmHg), Grade 3 (\>=100 mmHg). Data for worst-case post Baseline is reported. |
| Part 1: Number of Participants With Change From Baseline in Heart Rate | Median of 4 weeks of drug exposure | Heart rate was measured after restings for 5 minutes in semi-supine position. Data for participants with heart rate decreased to \< 60 beats per minute (bpm), normal or no change, increase to \> 100 bpm. Data for worst post Baseline were reported. |
| Part 1: Number of Participants With Change From Baseline in Temperature | Median of 4 weeks of drug exposure | Temperature was measured after resting for 5 minutes in semi-supine position. Data for participants with temperature decreased to \<=35 Celsius, normal or no change, increase to \>=38 Celsius at worst-case post Baseline is reported. |
| Part 1: Number of Participants With Change From Baseline in Respiratory Rate | Median of 4 weeks of drug exposure | Respiration rate was measured after resting for 5 minutes in semi-supine position. Data for worst case post-Baseline has been reported. Number of participants with respiratory rate decrease to \<12 and increase to \>25 has been reported. |
| Part 1: Number of Participants With Abnormal Electrocardiograms (ECGs) Findings | Median of 4 weeks of drug exposure | A single 12-lead ECG was performed in semi-recumbent or supine position after 5 minutes of rest for the participant. An ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and corrected QT intervals was used. Number of participants with any visit post-Baseline abnormal clinically significant findings and abnormal not clinically significant findings in ECG results has been reported. |
| Part 1: Number of Participants With Abnormal Physical Examinations | Median of 4 weeks of drug exposure | Data for participants with abnormal physical examinations parameters was planned to be recorded. |
| Part 2: Objective Response Rate of Participants | Up to 14 months | Objective response rate defined as the percentage of participants who achievied complete remission (CR), partial remission (PR), CRp (as per CR but platelet count \<100 x 10\^9/L) and morphologic leukemia free state per response criteria. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Number of Participants With Withdrawals Due to Toxicities | Up to 14 months | Participants were monitored from start of the study till the development of toxicity. The data for number of participants withdrawn due to toxicities has been presented. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1. |
| Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters | Up to 14 months | Data was not collected for Part 2 as the study was terminated early during Part 1. |
| Part 2: Number of Participants With Abnormal Hematology Parameters | Up to 14 months | Data was not collected for Part 2 as the study was terminated early during Part 1. |
| Part 2: Number of Participants With Abnormal Vital Signs | Up to 14 months | Data was not collected for Part 2 as the study was terminated early during Part 1. |
| Part 2: Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Up to 14 months | This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1. |
| Part 2: Number of Participants With Abnormal Physical Examinations | Up to 14 months | This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1. |
| Part 2: Clearance (CL) of GSK2879552 for Part 2 | Day 1 (pre-dose, 0.5 and 3 hours post dose), Days 4, 8 (pre-dose), Day 15 (pre-dose, 0.5, 1, 4, 6 hours), Weeks 4, 5, 6, 7, 8 and every 4 weeks up to Week 48 | This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1. |
| Part 2: Volume of Distribution of GSK2879552 for Part 2 | Day 1 (pre-dose, 0.5 and 3 hours post dose), Days 4, 8 (pre-dose), Day 15 (pre-dose, 0.5, 1, 4, 6 hours), Weeks 4, 5, 6, 7, 8 and every 4 weeks up to Week 48 | This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1. |
| Number of Participants With Abnormal Covariates: Part 2 | Up to 14 months | This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1. |
| Duration of Response: Part 2 | Up to 14 months | This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1. |
| Time to Time to Response: Part 2 | Up to 14 months | This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1. |
| Part 1: Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and From Time Zero (Pre-dose) Extrapolated to Infinite Time [(AUC(0-inf)] After Single Dose Administration | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 | Blood samples were collected at indicated time points. The Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis. NA indicates that data were not available as geometric co-efficient of variation could not be calculated for a single participant. |
| Progression-free Survival: Part 2 | Up to 14 months | This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1. |
| Part 1: AUC Over the Dosing Interval (0-tau) After Single Dose Administration | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 | Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. NA indicates that data were not available as geometric co-efficient could not be calculated for a single participant. |
| Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and AUC Over the Dosing Interval (0-tau) After Repeated Administration | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 15 | Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. NA indicates that data were not available as geometric coefficient of variation could not be calculated for a single participant. |
| Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK2879552 | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15 | Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. NA indicates that data were not available as geometric coefficient of variation could not be calculated for a single participant. |
| Part 1: Apparent Terminal Phase Half-life (t½) | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15 | Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. NA indicates that data were not available as geometric coefficient of variation could not be calculated for a single participant. |
| Part 1: Time of Occurrence of Cmax (Tmax) of GSK2879552 | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15 | Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. NA indicates that data were not available as standard deviation could not be calculated for a single participant. |
| Part 1: Accumulation Ratio for GSK2879552 | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15 | Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. Accumulation ratio was determined dividing AUC (0-tau) on Day 15 by AUC (0-tau) on Day 1. The ratio of accumulation of GSK2879552 was estimated by calculating the ratio of the geometric least squares (GLS) means of the AUC(0-tau) between Day 15 and Day 1 for all dose levels and the corresponding 90 percent confidence interval (CI) for each ratio. |
| Part 1:Time Invariance | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15 | Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. The time invariance of GSK2879552 was estimated by calculating the ratio of the GLS means of the AUC (0-tau) between Day 15 and Day 1 for all dose levels and the corresponding 90 percent CI for each ratio. |
| Part 1:Percentage of Participants With Objective Response | Median of 4 weeks drug response | Objective response rate is defined as the percentage of participants who achieved CR, PR, as per CR but platelet count \<100 x 10\^9/L and morphologic leukemia free state per response criteria. |
| Part 1: AUC(0-t), AUC (0-tau) and AUC(0-inf) of ATRA | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1and Day 15 | Blood samples were collected at indicated time points. The Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis. |
| Part 1: Cmax of ATRA | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15 | Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. |
| Part 1: Apparent Terminal Phase Half-life (t½) of ATRA | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15 | Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. |
| Part 1: Time of Occurrence of Cmax (Tmax) of ATRA | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15 | Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. |
| Part 2: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Up to 14 months | An AE is any untoward medical occurrence in a 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, 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. |
| Part 2: Number of Participants With AE Leading to Dose Reductions or Delays | Up to 14 months | The number of participants who had any dose reduction or delay have been presented. All dose reductions were due to AEs. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1. |
Countries
Australia, Canada, United States
Participant flow
Recruitment details
A total of 41 participants with relapsed/refractory acute myeloid leukemia (AML) were enrolled in Part 1 at different centers in Australia, Canada and United States. This study was planned to be conducted in 2 parts :Part 1 (dose escalation) and Part 2 (Expansion Cohort).
Pre-assignment details
This study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study and therefore, Part 2 was not conducted. There were no active participants on study when the study was terminated.
Participants by arm
| Arm | Count |
|---|---|
| Part 1:GSK2879552 1mg QD Participants received GSK2879552 1 mg orally QD in fasted condition with approximately 200 mL of water. | 1 |
| Part 1: GSK2879552 2mg QD Participants received GSK2879552 2 mg orally once daily in fasted condition with approximately 200 mL of water. | 2 |
| Part 1: GSK2879552 4mg QD Participants received GSK2879552 4 mg orally once daily in fasted condition with approximately 200 mL of water. | 7 |
| Part 1: GSK2879552 8mg QD Participants received GSK2879552 8 mg orally once daily in fasted condition with approximately 200 mL of water. | 5 |
| Part 1: GSK2879552 12mg QD Participants received GSK2879552 12 mg orally once daily in fasted condition with approximately 200 mL of water. | 6 |
| Part 1: GSK2879552 20mg QD Participants received GSK2879552 20 mg orally once daily in fasted condition with approximately 200 mL of water. | 4 |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day Participants received GSK2879552 2 mg capsule orally once daily in fasted condition with approximately 200 mL of water in combination with ATRA at a dose of 45 mg/m\^2/day. | 10 |
| Part 1: GSK2879552 20mg QD PK/PD Expansion Participants received GSK2879552 20 mg capsule orally once daily in fasted condition with approximately 200 mL of water in PK/PD Expansion cohort to collect adequate data on safety, PK or PD. | 6 |
| Part 2: Expansion Cohort In Part 2, participants were planned to receive the recommended Phase 2 dose of GSK2879552 orally once daily in fasted condition with approximately 200 mL of water alone or in combination with ATRA. | 0 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Part 1 (Median of 4 Weeks) | Adverse Event | 0 | 0 | 0 | 1 | 1 | 1 | 6 | 1 | 0 |
| Part 1 (Median of 4 Weeks) | Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 |
| Part 1 (Median of 4 Weeks) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 0 |
Baseline characteristics
| Characteristic | Part 1: GSK2879552 2mg QD | Part 1: GSK2879552 4mg QD | Part 1: GSK2879552 8mg QD | Part 1: GSK2879552 12mg QD | Part 1: GSK2879552 20mg QD | Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: GSK2879552 20mg QD PK/PD Expansion | Total | Part 1:GSK2879552 1mg QD | Part 2: Expansion Cohort |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 73.5 Years STANDARD_DEVIATION 2.12 | 64.3 Years STANDARD_DEVIATION 5.77 | 61.0 Years STANDARD_DEVIATION 13.96 | 71.7 Years STANDARD_DEVIATION 4.08 | 71.8 Years STANDARD_DEVIATION 4.03 | 63.1 Years STANDARD_DEVIATION 20.14 | 65.5 Years STANDARD_DEVIATION 19.07 | 66.1 Years STANDARD_DEVIATION 13.47 | 68.0 Years | — |
| Race/Ethnicity, Customized Asian - Central/South Asian Heritage | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 4 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 6 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 2 Participants | 4 Participants | 3 Participants | 2 Participants | 2 Participants | 6 Participants | 4 Participants | 24 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 3 Participants | 3 Participants | 2 Participants | 1 Participants | 3 Participants | 1 Participants | 13 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 2 Participants | 4 Participants | 3 Participants | 7 Participants | 5 Participants | 28 Participants | 1 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 2 | 1 / 7 | 0 / 5 | 3 / 6 | 1 / 4 | 2 / 10 | 1 / 6 | 0 / 0 |
| other Total, other adverse events | 1 / 1 | 2 / 2 | 6 / 7 | 5 / 5 | 6 / 6 | 4 / 4 | 10 / 10 | 6 / 6 | 0 / 0 |
| serious Total, serious adverse events | 1 / 1 | 2 / 2 | 7 / 7 | 5 / 5 | 6 / 6 | 3 / 4 | 8 / 10 | 5 / 6 | 0 / 0 |
Outcome results
Primary
Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range
Blood samples were collected to assess clinical chemistry parameters like urea/blood urea nitrogen (BUN), calcium, potassium, aspartate aminotransferase (AST), total bilirubin, direct bilirubin, creatinine, chloride, alanine aminotransferase (ALT), uric acid, glucose, total carbon dioxide (CO2), gamma glutamyl transferase (GGT), albumin, sodium, alkaline phosphatase, total protein, phosphate, lactate dehydrogenase (LDH). Laboratory values were as per local labs per site with own normal ranges. Values above range were reported as high and values below range as low. Data for worst case post Baseline is reported.
Time frame: Median of 4 weeks of drug exposure
Population: All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Chloride,to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Urea/BUN,to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Urea/BUN,to Low,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Chloride,to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Direct Bilirubin,to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | CO2/Bicarbonate,to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Lactate Dehydrogenase,to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Lactate Dehydrogenase,to High,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Direct Bilirubin,to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Total Protein,to Low,n=1,2,7,4,6,4,10,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | CO2/Bicarbonate,to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Total Protein,to High,n=1,2,7,4,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Lactate Dehydrogenase,to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Lactate Dehydrogenase,to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Urea/BUN,to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Direct Bilirubin,to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Chloride,to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Urea/BUN,to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Chloride,to High,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Direct Bilirubin,to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Total Protein,to High,n=1,2,7,4,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | CO2/Bicarbonate,to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Total Protein,to Low,n=1,2,7,4,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | CO2/Bicarbonate,to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Urea/BUN,to High,n=1,2,7,5,6,4,10,6 | 3 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | CO2/Bicarbonate,to High,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Total Protein,to Low,n=1,2,7,4,6,4,10,6 | 3 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Lactate Dehydrogenase,to Low,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Urea/BUN,to Low,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Lactate Dehydrogenase,to High,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Chloride,to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Direct Bilirubin,to High,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Chloride,to High,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | CO2/Bicarbonate,to Low,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Total Protein,to High,n=1,2,7,4,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Direct Bilirubin,to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Total Protein,to High,n=1,2,7,4,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Chloride,to High,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | CO2/Bicarbonate,to High,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Direct Bilirubin,to High,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Lactate Dehydrogenase,to Low,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | CO2/Bicarbonate,to Low,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Urea/BUN,to High,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Total Protein,to Low,n=1,2,7,4,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Chloride,to Low,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Direct Bilirubin,to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Lactate Dehydrogenase,to High,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Urea/BUN,to Low,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Lactate Dehydrogenase,to High,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Direct Bilirubin,to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Direct Bilirubin,to High,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Chloride,to Low,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Chloride,to High,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | CO2/Bicarbonate,to Low,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | CO2/Bicarbonate,to High,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Lactate Dehydrogenase,to Low,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Total Protein,to Low,n=1,2,7,4,6,4,10,6 | 4 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Total Protein,to High,n=1,2,7,4,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Urea/BUN,to Low,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Urea/BUN,to High,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Chloride,to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | CO2/Bicarbonate,to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Chloride,to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Total Protein,to High,n=1,2,7,4,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Urea/BUN,to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Direct Bilirubin,to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Lactate Dehydrogenase,to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | CO2/Bicarbonate,to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Direct Bilirubin,to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Total Protein,to Low,n=1,2,7,4,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Lactate Dehydrogenase,to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Urea/BUN,to Low,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | CO2/Bicarbonate,to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Lactate Dehydrogenase,to High,n=1,2,7,5,6,4,10,6 | 3 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | CO2/Bicarbonate,to Low,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Total Protein,to Low,n=1,2,7,4,6,4,10,6 | 3 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Chloride,to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Total Protein,to High,n=1,2,7,4,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Chloride,to Low,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Direct Bilirubin,to High,n=1,2,7,5,6,4,10,6 | 5 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Urea/BUN,to High,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Urea/BUN,to Low,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Direct Bilirubin,to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Lactate Dehydrogenase,to Low,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Lactate Dehydrogenase,to Low,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Total Protein,to Low,n=1,2,7,4,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | CO2/Bicarbonate,to High,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Urea/BUN,to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Urea/BUN,to High,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Chloride,to Low,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Direct Bilirubin,to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Total Protein,to High,n=1,2,7,4,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Lactate Dehydrogenase,to High,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Chloride,to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | Direct Bilirubin,to High,n=1,2,7,5,6,4,10,6 | 3 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range | CO2/Bicarbonate,to Low,n=1,2,7,5,6,4,10,6 | 2 Participants |
Primary
Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline
Blood samples were collected for analysis of clinical chemistry parameters based on common terminology criteria for adverse events (CTCAE) version 4.0, where Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life threatening consequences. Data for any increase in grade of worst-case on-therapy has been provided.
Time frame: Median of 4 weeks of drug exposure
Population: All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hyperkalemia,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | ALT, n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypoglycemia,n=0,1,7,5,6,4,9,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypoglycemia,n= 1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | GGT,n=1,2,7,5,3,1,8,3 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypernatremia, n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hyperglycemia,n= 0,1,7,5,6,4,9,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Phosphorus, n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hyponatremia, n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | AST, n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypercalcemia, n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | ALP, n=1,2,7,5,6,4, 10, 6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Creatinine,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypokalemia,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Albumin, n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Total bilirubin, n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hyperglycemia,n= 0,1,7,5,6,4,9,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Total bilirubin, n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypoglycemia,n= 1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypercalcemia, n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hyponatremia, n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hyperkalemia,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypoglycemia,n=0,1,7,5,6,4,9,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | GGT,n=1,2,7,5,3,1,8,3 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Albumin, n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Phosphorus, n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | ALT, n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypokalemia,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | ALP, n=1,2,7,5,6,4, 10, 6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Creatinine,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | AST, n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypernatremia, n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hyperkalemia,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypoglycemia,n=0,1,7,5,6,4,9,6 | 0 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | ALP, n=1,2,7,5,6,4, 10, 6 | 3 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Phosphorus, n=1,2,7,5,6,4,10,6 | 6 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | ALT, n=1,2,7,5,6,4,10,6 | 4 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Albumin, n=1,2,7,5,6,4,10,6 | 5 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | AST, n=1,2,7,5,6,4,10,6 | 3 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hyponatremia, n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Total bilirubin, n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypercalcemia, n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypoglycemia,n= 1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypernatremia, n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Creatinine,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | GGT,n=1,2,7,5,3,1,8,3 | 5 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypokalemia,n=1,2,7,5,6,4,10,6 | 3 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hyperglycemia,n= 0,1,7,5,6,4,9,6 | 4 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypernatremia, n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Total bilirubin, n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypoglycemia,n=0,1,7,5,6,4,9,6 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypoglycemia,n= 1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hyponatremia, n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hyperglycemia,n= 0,1,7,5,6,4,9,6 | 2 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | AST, n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Creatinine,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | ALT, n=1,2,7,5,6,4,10,6 | 3 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | GGT,n=1,2,7,5,3,1,8,3 | 4 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Phosphorus, n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypokalemia,n=1,2,7,5,6,4,10,6 | 4 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | ALP, n=1,2,7,5,6,4, 10, 6 | 2 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Albumin, n=1,2,7,5,6,4,10,6 | 3 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hyperkalemia,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypercalcemia, n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypercalcemia, n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | ALP, n=1,2,7,5,6,4, 10, 6 | 1 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hyperkalemia,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Albumin, n=1,2,7,5,6,4,10,6 | 4 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypoglycemia,n= 1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | GGT,n=1,2,7,5,3,1,8,3 | 2 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypernatremia, n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | AST, n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Total bilirubin, n=1,2,7,5,6,4,10,6 | 3 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hyponatremia, n=1,2,7,5,6,4,10,6 | 5 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hyperglycemia,n= 0,1,7,5,6,4,9,6 | 1 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypoglycemia,n=0,1,7,5,6,4,9,6 | 0 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Creatinine,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Phosphorus, n=1,2,7,5,6,4,10,6 | 5 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | ALT, n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypokalemia,n=1,2,7,5,6,4,10,6 | 3 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | AST, n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Albumin, n=1,2,7,5,6,4,10,6 | 4 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | ALP, n=1,2,7,5,6,4, 10, 6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | ALT, n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Total bilirubin, n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypercalcemia, n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypoglycemia,n= 1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Creatinine,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | GGT,n=1,2,7,5,3,1,8,3 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hyperglycemia,n= 0,1,7,5,6,4,9,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypoglycemia,n=0,1,7,5,6,4,9,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hyperkalemia,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypokalemia,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypernatremia, n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hyponatremia, n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Phosphorus, n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Creatinine,n=1,2,7,5,6,4,10,6 | 4 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Total bilirubin, n=1,2,7,5,6,4,10,6 | 4 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hyperglycemia,n= 0,1,7,5,6,4,9,6 | 4 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | AST, n=1,2,7,5,6,4,10,6 | 3 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypoglycemia,n= 1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Phosphorus, n=1,2,7,5,6,4,10,6 | 3 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hyponatremia, n=1,2,7,5,6,4,10,6 | 5 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Albumin, n=1,2,7,5,6,4,10,6 | 6 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | ALT, n=1,2,7,5,6,4,10,6 | 5 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypercalcemia, n=1,2,7,5,6,4,10,6 | 3 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | ALP, n=1,2,7,5,6,4, 10, 6 | 3 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypokalemia,n=1,2,7,5,6,4,10,6 | 6 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypoglycemia,n=0,1,7,5,6,4,9,6 | 1 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypernatremia, n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hyperkalemia,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | GGT,n=1,2,7,5,3,1,8,3 | 5 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hyperkalemia,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | GGT,n=1,2,7,5,3,1,8,3 | 2 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Creatinine,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypokalemia,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypoglycemia,n= 1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypercalcemia, n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Phosphorus, n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypernatremia, n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Total bilirubin, n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | AST, n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | ALT, n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hyponatremia, n=1,2,7,5,6,4,10,6 | 3 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | ALP, n=1,2,7,5,6,4, 10, 6 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hypoglycemia,n=0,1,7,5,6,4,9,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Albumin, n=1,2,7,5,6,4,10,6 | 3 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline | Hyperglycemia,n= 0,1,7,5,6,4,9,6 | 4 Participants |
Primary
Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range
Blood samples were collected to assess hematology parameters like mean corpuscle hemoglobin concentration (MCHC), mean corpuscle hemoglobin (MCH), mean corpuscle volume (MCV) mean platelet volume (MPV), basophils, eosinophils, hematocrit, hemoglobin, lymphocytes, monocytes, platelet count, Red blood cell (RBC) count, reticulocytes, White Blood Cell (WBC) count. Laboratory values were as per local labs per site with own normal ranges. Values above range were reported as high and values below range as low. Data for worst post Baseline were reported. NA indicates that data were not available as standard deviation could not be calculated for a single participant.
Time frame: Median of 4 weeks of drug exposure
Population: All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1:GSK2879552 1mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Monocytes, to Low,n=1,2,7,4,2,2,10,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Monocytes, to High,n=1,2,7,4,2,2,10,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | RBC, to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCHC, to Low,n=1,2,7,5,3,2,10,6 | 1 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Reticulocytes, to Low,n=1,2,7,4,2,2,7,5 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Reticulocytes, to High,n=1,2,7,4,2,2,7,5 | 1 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Eosinophils, to High,n=1,2,7,4,2,2,8,5 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCH, to Low,n=1,2,7,5,3,2,10,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCV, to High,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCHC, to High,n=1,2,7,5,3,2,10,6 | 1 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Hematocrit, to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCH, to High,n=1,2,7,5,3,2,10,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Eosinophils, to Low,n=1,2,7,4,2,2,8,5 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | RBC, to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Basophils, to Low,n=1,2,7,4,2,2,9,5 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Basophils, to High,n=1,2,7,4,2,2,9,5 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCV, to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Hematocrit, to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCV, to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Hematocrit, to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCHC, to Low,n=1,2,7,5,3,2,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | RBC, to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Hematocrit, to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCH, to Low,n=1,2,7,5,3,2,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Reticulocytes, to High,n=1,2,7,4,2,2,7,5 | 1 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Monocytes, to Low,n=1,2,7,4,2,2,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCH, to High,n=1,2,7,5,3,2,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Eosinophils, to Low,n=1,2,7,4,2,2,8,5 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCV, to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Basophils, to High,n=1,2,7,4,2,2,9,5 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Reticulocytes, to Low,n=1,2,7,4,2,2,7,5 | 2 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCHC, to High,n=1,2,7,5,3,2,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Eosinophils, to High,n=1,2,7,4,2,2,8,5 | 1 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Basophils, to Low,n=1,2,7,4,2,2,9,5 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | RBC, to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Monocytes, to High,n=1,2,7,4,2,2,10,6 | 1 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | RBC, to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCH, to High,n=1,2,7,5,3,2,10,6 | 0 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCV, to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCV, to Low,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Basophils, to Low,n=1,2,7,4,2,2,9,5 | 2 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Reticulocytes, to Low,n=1,2,7,4,2,2,7,5 | 5 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Eosinophils, to Low,n=1,2,7,4,2,2,8,5 | 2 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Eosinophils, to High,n=1,2,7,4,2,2,8,5 | 1 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Reticulocytes, to High,n=1,2,7,4,2,2,7,5 | 1 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | RBC, to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Hematocrit, to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Hematocrit, to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCHC, to Low,n=1,2,7,5,3,2,10,6 | 0 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Monocytes, to High,n=1,2,7,4,2,2,10,6 | 4 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCHC, to High,n=1,2,7,5,3,2,10,6 | 3 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Monocytes, to Low,n=1,2,7,4,2,2,10,6 | 2 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCH, to Low,n=1,2,7,5,3,2,10,6 | 0 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Basophils, to High,n=1,2,7,4,2,2,9,5 | 1 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCH, to High,n=1,2,7,5,3,2,10,6 | 1 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCHC, to Low,n=1,2,7,5,3,2,10,6 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | RBC, to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Monocytes, to High,n=1,2,7,4,2,2,10,6 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCH, to Low,n=1,2,7,5,3,2,10,6 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Reticulocytes, to High,n=1,2,7,4,2,2,7,5 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Eosinophils, to High,n=1,2,7,4,2,2,8,5 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | RBC, to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCV, to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCHC, to High,n=1,2,7,5,3,2,10,6 | 2 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Basophils, to Low,n=1,2,7,4,2,2,9,5 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Eosinophils, to Low,n=1,2,7,4,2,2,8,5 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Monocytes, to Low,n=1,2,7,4,2,2,10,6 | 1 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Basophils, to High,n=1,2,7,4,2,2,9,5 | 2 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Reticulocytes, to Low,n=1,2,7,4,2,2,7,5 | 1 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCV, to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Hematocrit, to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Nucleated RBC, to Low,n=0,0,0,1,1,0,1,0 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MPV, to High,n=0,0,0,3,6,3,7,6 | 1 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MPV, to Low,n=0,0,0,3,6,3,7,6 | 1 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Nucleated RBC, to High,n=0,0,0,1,1,0,1,0 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Hematocrit, to Low,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Hematocrit, to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Basophils, to Low,n=1,2,7,4,2,2,9,5 | 0 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Basophils, to High,n=1,2,7,4,2,2,9,5 | 1 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Eosinophils, to Low,n=1,2,7,4,2,2,8,5 | 1 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Eosinophils, to High,n=1,2,7,4,2,2,8,5 | 0 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Hemoglobin, to Low,n=0,0,0,0,2,0,0,1 | 0 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Hemoglobin, to High,n=0,0,0,0,2,0,0,1 | 0 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Hematocrit, to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCHC, to Low,n=1,2,7,5,3,2,10,6 | 1 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCHC, to High,n=1,2,7,5,3,2,10,6 | 0 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCH, to Low,n=1,2,7,5,3,2,10,6 | 0 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCH, to High,n=1,2,7,5,3,2,10,6 | 0 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCV, to Low,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCV, to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Monocytes, to Low,n=1,2,7,4,2,2,10,6 | 0 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Monocytes, to High,n=1,2,7,4,2,2,10,6 | 1 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MPV, to Low,n=0,0,0,3,6,3,7,6 | 1 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MPV, to High,n=0,0,0,3,6,3,7,6 | 2 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Nucleated RBC, to Low,n=0,0,0,1,1,0,1,0 | 0 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Nucleated RBC, to High,n=0,0,0,1,1,0,1,0 | 0 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | RBC, to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | RBC, to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Reticulocytes, to Low,n=1,2,7,4,2,2,7,5 | 2 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Reticulocytes, to High,n=1,2,7,4,2,2,7,5 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Reticulocytes, to High,n=1,2,7,4,2,2,7,5 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Reticulocytes, to Low,n=1,2,7,4,2,2,7,5 | 1 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Eosinophils, to High,n=1,2,7,4,2,2,8,5 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MPV, to High,n=0,0,0,3,6,3,7,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCHC, to High,n=1,2,7,5,3,2,10,6 | 1 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | RBC, to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Hematocrit, to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCH, to High,n=1,2,7,5,3,2,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCV, to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Hematocrit, to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Basophils, to Low,n=1,2,7,4,2,2,9,5 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCHC, to Low,n=1,2,7,5,3,2,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCV, to Low,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Monocytes, to High,n=1,2,7,4,2,2,10,6 | 1 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Monocytes, to Low,n=1,2,7,4,2,2,10,6 | 1 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Eosinophils, to Low,n=1,2,7,4,2,2,8,5 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | RBC, to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Basophils, to High,n=1,2,7,4,2,2,9,5 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MPV, to Low,n=0,0,0,3,6,3,7,6 | 1 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCH, to Low,n=1,2,7,5,3,2,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCH, to Low,n=1,2,7,5,3,2,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCHC, to High,n=1,2,7,5,3,2,10,6 | 2 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Reticulocytes, to Low,n=1,2,7,4,2,2,7,5 | 2 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Monocytes, to Low,n=1,2,7,4,2,2,10,6 | 2 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCHC, to Low,n=1,2,7,5,3,2,10,6 | 1 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Monocytes, to High,n=1,2,7,4,2,2,10,6 | 2 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MPV, to Low,n=0,0,0,3,6,3,7,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Hematocrit, to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MPV, to High,n=0,0,0,3,6,3,7,6 | 3 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Basophils, to Low,n=1,2,7,4,2,2,9,5 | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Nucleated RBC, to Low,n=0,0,0,1,1,0,1,0 | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Nucleated RBC, to High,n=0,0,0,1,1,0,1,0 | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Hematocrit, to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | RBC, to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Eosinophils, to High,n=1,2,7,4,2,2,8,5 | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | RBC, to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Eosinophils, to Low,n=1,2,7,4,2,2,8,5 | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Basophils, to High,n=1,2,7,4,2,2,9,5 | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Reticulocytes, to High,n=1,2,7,4,2,2,7,5 | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCV, to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCH, to High,n=1,2,7,5,3,2,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCV, to High,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Basophils, to Low,n=1,2,7,4,2,2,9,5 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Eosinophils, to Low,n=1,2,7,4,2,2,8,5 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MPV, to Low,n=0,0,0,3,6,3,7,6 | 1 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Hematocrit, to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCV, to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | RBC, to High,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCHC, to Low,n=1,2,7,5,3,2,10,6 | 1 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Monocytes, to High,n=1,2,7,4,2,2,10,6 | 2 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Basophils, to High,n=1,2,7,4,2,2,9,5 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCH, to Low,n=1,2,7,5,3,2,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Monocytes, to Low,n=1,2,7,4,2,2,10,6 | 1 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Reticulocytes, to Low,n=1,2,7,4,2,2,7,5 | 1 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCHC, to High,n=1,2,7,5,3,2,10,6 | 1 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Hematocrit, to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Hemoglobin, to High,n=0,0,0,0,2,0,0,1 | 1 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Hemoglobin, to Low,n=0,0,0,0,2,0,0,1 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Reticulocytes, to High,n=1,2,7,4,2,2,7,5 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MPV, to High,n=0,0,0,3,6,3,7,6 | 4 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCV, to Low,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | RBC, to Low,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | Eosinophils, to High,n=1,2,7,4,2,2,8,5 | 1 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range | MCH, to High,n=1,2,7,5,3,2,10,6 | 0 Participants |
Primary
Number of Participants With Hematology Toxicity Grade Changes From Baseline
Blood samples were collected for analysis of hematology parameters based on common terminology criteria for adverse events (CTCAE) version 4.0, where Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life threatening consequences. Data for any grade increase worst-case on-therapy has been provided.
Time frame: Median of 4 weeks of drug exposure
Population: All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1:GSK2879552 1mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Total Neu,n=1,2,7,4,2,2,10,6 | 1 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Platelet,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Lymph increase,n=1,2,7,4,2,2,10,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Hg increase,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Hg anemia,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Lymph decrease,n=1,2,7,4,2,2,10,6 | 1 Participants |
| Part 1:GSK2879552 1mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | WBC,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | WBC,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Total Neu,n=1,2,7,4,2,2,10,6 | 2 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Hg anemia,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Lymph increase,n=1,2,7,4,2,2,10,6 | 1 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Lymph decrease,n=1,2,7,4,2,2,10,6 | 2 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Hg increase,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Platelet,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Total Neu,n=1,2,7,4,2,2,10,6 | 1 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | WBC,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Lymph decrease,n=1,2,7,4,2,2,10,6 | 2 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Hg anemia,n=1,2,7,5,6,4,10,6 | 5 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Hg increase,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Platelet,n=1,2,7,5,6,4,10,6 | 4 Participants |
| Part 1: GSK2879552 4mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Lymph increase,n=1,2,7,4,2,2,10,6 | 1 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Lymph decrease,n=1,2,7,4,2,2,10,6 | 3 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | WBC,n=1,2,7,5,6,4,10,6 | 4 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Hg anemia,n=1,2,7,5,6,4,10,6 | 4 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Platelet,n=1,2,7,5,6,4,10,6 | 3 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Lymph increase,n=1,2,7,4,2,2,10,6 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Hg increase,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Total Neu,n=1,2,7,4,2,2,10,6 | 1 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Lymph decrease,n=1,2,7,4,2,2,10,6 | 1 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Hg increase,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Hg anemia,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Lymph increase,n=1,2,7,4,2,2,10,6 | 0 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Total Neu,n=1,2,7,4,2,2,10,6 | 1 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Platelet,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 12mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | WBC,n=1,2,7,5,6,4,10,6 | 5 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Lymph decrease,n=1,2,7,4,2,2,10,6 | 2 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | WBC,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Total Neu,n=1,2,7,4,2,2,10,6 | 1 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Lymph increase,n=1,2,7,4,2,2,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Platelet,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Hg anemia,n=1,2,7,5,6,4,10,6 | 2 Participants |
| Part 1: GSK2879552 20mg QD | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Hg increase,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Hg anemia,n=1,2,7,5,6,4,10,6 | 4 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Hg increase,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Platelet,n=1,2,7,5,6,4,10,6 | 3 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Total Neu,n=1,2,7,4,2,2,10,6 | 1 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Toxicity Grade Changes From Baseline | WBC,n=1,2,7,5,6,4,10,6 | 5 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Lymph increase,n=1,2,7,4,2,2,10,6 | 3 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Lymph decrease,n=1,2,7,4,2,2,10,6 | 5 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Toxicity Grade Changes From Baseline | WBC,n=1,2,7,5,6,4,10,6 | 1 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Lymph decrease,n=1,2,7,4,2,2,10,6 | 2 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Platelet,n=1,2,7,5,6,4,10,6 | 3 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Hg increase,n=1,2,7,5,6,4,10,6 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Lymph increase,n=1,2,7,4,2,2,10,6 | 1 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Total Neu,n=1,2,7,4,2,2,10,6 | 1 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Number of Participants With Hematology Toxicity Grade Changes From Baseline | Hg anemia,n=1,2,7,5,6,4,10,6 | 3 Participants |
Primary
Part 1: Number of Participants With Abnormal Electrocardiograms (ECGs) Findings
A single 12-lead ECG was performed in semi-recumbent or supine position after 5 minutes of rest for the participant. An ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and corrected QT intervals was used. Number of participants with any visit post-Baseline abnormal clinically significant findings and abnormal not clinically significant findings in ECG results has been reported.
Time frame: Median of 4 weeks of drug exposure
Population: All Treated Subjects Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1:GSK2879552 1mg QD | Part 1: Number of Participants With Abnormal Electrocardiograms (ECGs) Findings | Abnormal - not clinically significant | 1 Participants |
| Part 1:GSK2879552 1mg QD | Part 1: Number of Participants With Abnormal Electrocardiograms (ECGs) Findings | Abnormal - clinically significant | 0 Participants |
| Part 1: GSK2879552 2mg QD | Part 1: Number of Participants With Abnormal Electrocardiograms (ECGs) Findings | Abnormal - not clinically significant | 2 Participants |
| Part 1: GSK2879552 2mg QD | Part 1: Number of Participants With Abnormal Electrocardiograms (ECGs) Findings | Abnormal - clinically significant | 0 Participants |
| Part 1: GSK2879552 4mg QD | Part 1: Number of Participants With Abnormal Electrocardiograms (ECGs) Findings | Abnormal - not clinically significant | 7 Participants |
| Part 1: GSK2879552 4mg QD | Part 1: Number of Participants With Abnormal Electrocardiograms (ECGs) Findings | Abnormal - clinically significant | 0 Participants |
| Part 1: GSK2879552 8mg QD | Part 1: Number of Participants With Abnormal Electrocardiograms (ECGs) Findings | Abnormal - not clinically significant | 4 Participants |
| Part 1: GSK2879552 8mg QD | Part 1: Number of Participants With Abnormal Electrocardiograms (ECGs) Findings | Abnormal - clinically significant | 0 Participants |
| Part 1: GSK2879552 12mg QD | Part 1: Number of Participants With Abnormal Electrocardiograms (ECGs) Findings | Abnormal - not clinically significant | 4 Participants |
| Part 1: GSK2879552 12mg QD | Part 1: Number of Participants With Abnormal Electrocardiograms (ECGs) Findings | Abnormal - clinically significant | 1 Participants |
| Part 1: GSK2879552 20mg QD | Part 1: Number of Participants With Abnormal Electrocardiograms (ECGs) Findings | Abnormal - not clinically significant | 2 Participants |
| Part 1: GSK2879552 20mg QD | Part 1: Number of Participants With Abnormal Electrocardiograms (ECGs) Findings | Abnormal - clinically significant | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Number of Participants With Abnormal Electrocardiograms (ECGs) Findings | Abnormal - clinically significant | 2 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Number of Participants With Abnormal Electrocardiograms (ECGs) Findings | Abnormal - not clinically significant | 4 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Number of Participants With Abnormal Electrocardiograms (ECGs) Findings | Abnormal - not clinically significant | 6 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Number of Participants With Abnormal Electrocardiograms (ECGs) Findings | Abnormal - clinically significant | 1 Participants |
Primary
Part 1: Number of Participants With Abnormal Physical Examinations
Data for participants with abnormal physical examinations parameters was planned to be recorded.
Time frame: Median of 4 weeks of drug exposure
Population: All Treated Subjects Population. The data was not collected as it was not captured within the case report form (CRF).
Primary
Part 1: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
An AE is any untoward medical occurrence in a 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, is a congenital anomaly/ birth defect, other situations and is associated with liver injury or impaired liver function.
Time frame: Median of 4 weeks of drug exposure
Population: All Treated Subjects Population comprised of all participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1:GSK2879552 1mg QD | Part 1: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | All AEs | 1 Participants |
| Part 1:GSK2879552 1mg QD | Part 1: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | All SAEs | 1 Participants |
| Part 1: GSK2879552 2mg QD | Part 1: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | All AEs | 2 Participants |
| Part 1: GSK2879552 2mg QD | Part 1: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | All SAEs | 2 Participants |
| Part 1: GSK2879552 4mg QD | Part 1: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | All AEs | 7 Participants |
| Part 1: GSK2879552 4mg QD | Part 1: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | All SAEs | 7 Participants |
| Part 1: GSK2879552 8mg QD | Part 1: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | All AEs | 5 Participants |
| Part 1: GSK2879552 8mg QD | Part 1: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | All SAEs | 5 Participants |
| Part 1: GSK2879552 12mg QD | Part 1: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | All AEs | 6 Participants |
| Part 1: GSK2879552 12mg QD | Part 1: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | All SAEs | 6 Participants |
| Part 1: GSK2879552 20mg QD | Part 1: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | All AEs | 4 Participants |
| Part 1: GSK2879552 20mg QD | Part 1: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | All SAEs | 3 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | All SAEs | 8 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | All AEs | 10 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | All AEs | 6 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | All SAEs | 5 Participants |
Primary
Part 1: Number of Participants With AE Leading to Dose Reductions or Delays
The number of participants who had any dose reduction or delay have been presented.
Time frame: Median of 4 weeks of drug exposure
Population: All Treated Subjects Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1:GSK2879552 1mg QD | Part 1: Number of Participants With AE Leading to Dose Reductions or Delays | AEs leading to dose reduction | 0 Participants |
| Part 1:GSK2879552 1mg QD | Part 1: Number of Participants With AE Leading to Dose Reductions or Delays | AEs leading to dose interruption/delay | 0 Participants |
| Part 1: GSK2879552 2mg QD | Part 1: Number of Participants With AE Leading to Dose Reductions or Delays | AEs leading to dose reduction | 0 Participants |
| Part 1: GSK2879552 2mg QD | Part 1: Number of Participants With AE Leading to Dose Reductions or Delays | AEs leading to dose interruption/delay | 0 Participants |
| Part 1: GSK2879552 4mg QD | Part 1: Number of Participants With AE Leading to Dose Reductions or Delays | AEs leading to dose reduction | 0 Participants |
| Part 1: GSK2879552 4mg QD | Part 1: Number of Participants With AE Leading to Dose Reductions or Delays | AEs leading to dose interruption/delay | 2 Participants |
| Part 1: GSK2879552 8mg QD | Part 1: Number of Participants With AE Leading to Dose Reductions or Delays | AEs leading to dose reduction | 0 Participants |
| Part 1: GSK2879552 8mg QD | Part 1: Number of Participants With AE Leading to Dose Reductions or Delays | AEs leading to dose interruption/delay | 3 Participants |
| Part 1: GSK2879552 12mg QD | Part 1: Number of Participants With AE Leading to Dose Reductions or Delays | AEs leading to dose reduction | 0 Participants |
| Part 1: GSK2879552 12mg QD | Part 1: Number of Participants With AE Leading to Dose Reductions or Delays | AEs leading to dose interruption/delay | 5 Participants |
| Part 1: GSK2879552 20mg QD | Part 1: Number of Participants With AE Leading to Dose Reductions or Delays | AEs leading to dose reduction | 0 Participants |
| Part 1: GSK2879552 20mg QD | Part 1: Number of Participants With AE Leading to Dose Reductions or Delays | AEs leading to dose interruption/delay | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Number of Participants With AE Leading to Dose Reductions or Delays | AEs leading to dose interruption/delay | 6 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Number of Participants With AE Leading to Dose Reductions or Delays | AEs leading to dose reduction | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Number of Participants With AE Leading to Dose Reductions or Delays | AEs leading to dose reduction | 1 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Number of Participants With AE Leading to Dose Reductions or Delays | AEs leading to dose interruption/delay | 1 Participants |
Primary
Part 1: Number of Participants With Change From Baseline in Heart Rate
Heart rate was measured after restings for 5 minutes in semi-supine position. Data for participants with heart rate decreased to \< 60 beats per minute (bpm), normal or no change, increase to \> 100 bpm. Data for worst post Baseline were reported.
Time frame: Median of 4 weeks of drug exposure
Population: All Treated Subjects Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1:GSK2879552 1mg QD | Part 1: Number of Participants With Change From Baseline in Heart Rate | Change to Normal or No Change | 0 Participants |
| Part 1:GSK2879552 1mg QD | Part 1: Number of Participants With Change From Baseline in Heart Rate | Increase to >100 | 1 Participants |
| Part 1:GSK2879552 1mg QD | Part 1: Number of Participants With Change From Baseline in Heart Rate | Decrease to <60 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Part 1: Number of Participants With Change From Baseline in Heart Rate | Change to Normal or No Change | 2 Participants |
| Part 1: GSK2879552 2mg QD | Part 1: Number of Participants With Change From Baseline in Heart Rate | Decrease to <60 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Part 1: Number of Participants With Change From Baseline in Heart Rate | Increase to >100 | 0 Participants |
| Part 1: GSK2879552 4mg QD | Part 1: Number of Participants With Change From Baseline in Heart Rate | Increase to >100 | 6 Participants |
| Part 1: GSK2879552 4mg QD | Part 1: Number of Participants With Change From Baseline in Heart Rate | Decrease to <60 | 1 Participants |
| Part 1: GSK2879552 4mg QD | Part 1: Number of Participants With Change From Baseline in Heart Rate | Change to Normal or No Change | 1 Participants |
| Part 1: GSK2879552 8mg QD | Part 1: Number of Participants With Change From Baseline in Heart Rate | Decrease to <60 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Part 1: Number of Participants With Change From Baseline in Heart Rate | Change to Normal or No Change | 4 Participants |
| Part 1: GSK2879552 8mg QD | Part 1: Number of Participants With Change From Baseline in Heart Rate | Increase to >100 | 1 Participants |
| Part 1: GSK2879552 12mg QD | Part 1: Number of Participants With Change From Baseline in Heart Rate | Increase to >100 | 2 Participants |
| Part 1: GSK2879552 12mg QD | Part 1: Number of Participants With Change From Baseline in Heart Rate | Change to Normal or No Change | 4 Participants |
| Part 1: GSK2879552 12mg QD | Part 1: Number of Participants With Change From Baseline in Heart Rate | Decrease to <60 | 1 Participants |
| Part 1: GSK2879552 20mg QD | Part 1: Number of Participants With Change From Baseline in Heart Rate | Decrease to <60 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Part 1: Number of Participants With Change From Baseline in Heart Rate | Change to Normal or No Change | 4 Participants |
| Part 1: GSK2879552 20mg QD | Part 1: Number of Participants With Change From Baseline in Heart Rate | Increase to >100 | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Number of Participants With Change From Baseline in Heart Rate | Change to Normal or No Change | 5 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Number of Participants With Change From Baseline in Heart Rate | Decrease to <60 | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Number of Participants With Change From Baseline in Heart Rate | Increase to >100 | 5 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Number of Participants With Change From Baseline in Heart Rate | Decrease to <60 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Number of Participants With Change From Baseline in Heart Rate | Increase to >100 | 3 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Number of Participants With Change From Baseline in Heart Rate | Change to Normal or No Change | 3 Participants |
Primary
Part 1: Number of Participants With Change From Baseline in Respiratory Rate
Respiration rate was measured after resting for 5 minutes in semi-supine position. Data for worst case post-Baseline has been reported. Number of participants with respiratory rate decrease to \<12 and increase to \>25 has been reported.
Time frame: Median of 4 weeks of drug exposure
Population: All Treated Subjects Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1:GSK2879552 1mg QD | Part 1: Number of Participants With Change From Baseline in Respiratory Rate | Decrease to <12 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Part 1: Number of Participants With Change From Baseline in Respiratory Rate | Increase to >25 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Part 1: Number of Participants With Change From Baseline in Respiratory Rate | Decrease to <12 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Part 1: Number of Participants With Change From Baseline in Respiratory Rate | Increase to >25 | 0 Participants |
| Part 1: GSK2879552 4mg QD | Part 1: Number of Participants With Change From Baseline in Respiratory Rate | Decrease to <12 | 0 Participants |
| Part 1: GSK2879552 4mg QD | Part 1: Number of Participants With Change From Baseline in Respiratory Rate | Increase to >25 | 2 Participants |
| Part 1: GSK2879552 8mg QD | Part 1: Number of Participants With Change From Baseline in Respiratory Rate | Decrease to <12 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Part 1: Number of Participants With Change From Baseline in Respiratory Rate | Increase to >25 | 0 Participants |
| Part 1: GSK2879552 12mg QD | Part 1: Number of Participants With Change From Baseline in Respiratory Rate | Decrease to <12 | 0 Participants |
| Part 1: GSK2879552 12mg QD | Part 1: Number of Participants With Change From Baseline in Respiratory Rate | Increase to >25 | 1 Participants |
| Part 1: GSK2879552 20mg QD | Part 1: Number of Participants With Change From Baseline in Respiratory Rate | Decrease to <12 | 1 Participants |
| Part 1: GSK2879552 20mg QD | Part 1: Number of Participants With Change From Baseline in Respiratory Rate | Increase to >25 | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Number of Participants With Change From Baseline in Respiratory Rate | Increase to >25 | 1 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Number of Participants With Change From Baseline in Respiratory Rate | Decrease to <12 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Number of Participants With Change From Baseline in Respiratory Rate | Decrease to <12 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Number of Participants With Change From Baseline in Respiratory Rate | Increase to >25 | 0 Participants |
Primary
Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP and DBP were measured after resting for 5 minutes in semi-supine position. Vital signs were graded according to Common Toxicity Criteria for Adverse Events (CTCAE) version 4. An increase is defined as an increase in CTCAE grade relative to Baseline grade. For SBP Grade 0 (\<120 millimeters of mercury \[mmHg\]), Grade 1 (120-139 mmHg), Grade 2 (140-159 mmHg), Grade 3 (\>=160 mmHg). For DBP Grade 0 (\<80 mmHg), Grade 1 (80-89 mmHg), Grade 2 (90-99 mmHg), Grade 3 (\>=100 mmHg). Data for worst-case post Baseline is reported.
Time frame: Median of 4 weeks of drug exposure
Population: All Treated Subjects Population. Only those participants with available data at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1:GSK2879552 1mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Increase to Grade 3;n=1, 2, 3, 2, 4, 1, 3, 2 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Increase to Grade 3;n=1, 1, 3, 4, 6, 2, 5, 3 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Any Grade Increase; n=1, 1, 3, 4, 6, 2, 5, 3 | 1 Participants |
| Part 1:GSK2879552 1mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Increase to Grade 2;n=1, 2, 3, 2, 4, 1, 3, 2 | 1 Participants |
| Part 1:GSK2879552 1mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Increase to Grade 2;n=1, 1, 3, 4, 6, 2, 5, 3 | 1 Participants |
| Part 1:GSK2879552 1mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Any Grade Increase;n=1, 2, 3, 2, 4, 1, 3, 2 | 1 Participants |
| Part 1: GSK2879552 2mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Any Grade Increase; n=1, 1, 3, 4, 6, 2, 5, 3 | 1 Participants |
| Part 1: GSK2879552 2mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Increase to Grade 2;n=1, 2, 3, 2, 4, 1, 3, 2 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Increase to Grade 2;n=1, 1, 3, 4, 6, 2, 5, 3 | 1 Participants |
| Part 1: GSK2879552 2mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Increase to Grade 3;n=1, 1, 3, 4, 6, 2, 5, 3 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Increase to Grade 3;n=1, 2, 3, 2, 4, 1, 3, 2 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Any Grade Increase;n=1, 2, 3, 2, 4, 1, 3, 2 | 2 Participants |
| Part 1: GSK2879552 4mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Increase to Grade 3;n=1, 2, 3, 2, 4, 1, 3, 2 | 0 Participants |
| Part 1: GSK2879552 4mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Increase to Grade 3;n=1, 1, 3, 4, 6, 2, 5, 3 | 0 Participants |
| Part 1: GSK2879552 4mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Any Grade Increase; n=1, 1, 3, 4, 6, 2, 5, 3 | 3 Participants |
| Part 1: GSK2879552 4mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Any Grade Increase;n=1, 2, 3, 2, 4, 1, 3, 2 | 3 Participants |
| Part 1: GSK2879552 4mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Increase to Grade 2;n=1, 1, 3, 4, 6, 2, 5, 3 | 1 Participants |
| Part 1: GSK2879552 4mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Increase to Grade 2;n=1, 2, 3, 2, 4, 1, 3, 2 | 1 Participants |
| Part 1: GSK2879552 8mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Increase to Grade 3;n=1, 2, 3, 2, 4, 1, 3, 2 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Any Grade Increase;n=1, 2, 3, 2, 4, 1, 3, 2 | 2 Participants |
| Part 1: GSK2879552 8mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Increase to Grade 2;n=1, 2, 3, 2, 4, 1, 3, 2 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Increase to Grade 3;n=1, 1, 3, 4, 6, 2, 5, 3 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Increase to Grade 2;n=1, 1, 3, 4, 6, 2, 5, 3 | 2 Participants |
| Part 1: GSK2879552 8mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Any Grade Increase; n=1, 1, 3, 4, 6, 2, 5, 3 | 4 Participants |
| Part 1: GSK2879552 12mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Any Grade Increase;n=1, 2, 3, 2, 4, 1, 3, 2 | 4 Participants |
| Part 1: GSK2879552 12mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Increase to Grade 2;n=1, 1, 3, 4, 6, 2, 5, 3 | 2 Participants |
| Part 1: GSK2879552 12mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Increase to Grade 3;n=1, 1, 3, 4, 6, 2, 5, 3 | 1 Participants |
| Part 1: GSK2879552 12mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Any Grade Increase; n=1, 1, 3, 4, 6, 2, 5, 3 | 6 Participants |
| Part 1: GSK2879552 12mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Increase to Grade 2;n=1, 2, 3, 2, 4, 1, 3, 2 | 2 Participants |
| Part 1: GSK2879552 12mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Increase to Grade 3;n=1, 2, 3, 2, 4, 1, 3, 2 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Increase to Grade 2;n=1, 2, 3, 2, 4, 1, 3, 2 | 1 Participants |
| Part 1: GSK2879552 20mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Increase to Grade 3;n=1, 1, 3, 4, 6, 2, 5, 3 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Increase to Grade 3;n=1, 2, 3, 2, 4, 1, 3, 2 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Any Grade Increase;n=1, 2, 3, 2, 4, 1, 3, 2 | 1 Participants |
| Part 1: GSK2879552 20mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Any Grade Increase; n=1, 1, 3, 4, 6, 2, 5, 3 | 2 Participants |
| Part 1: GSK2879552 20mg QD | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Increase to Grade 2;n=1, 1, 3, 4, 6, 2, 5, 3 | 1 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Any Grade Increase;n=1, 2, 3, 2, 4, 1, 3, 2 | 3 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Any Grade Increase; n=1, 1, 3, 4, 6, 2, 5, 3 | 5 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Increase to Grade 2;n=1, 2, 3, 2, 4, 1, 3, 2 | 2 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Increase to Grade 3;n=1, 1, 3, 4, 6, 2, 5, 3 | 2 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Increase to Grade 2;n=1, 1, 3, 4, 6, 2, 5, 3 | 4 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Increase to Grade 3;n=1, 2, 3, 2, 4, 1, 3, 2 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Increase to Grade 3;n=1, 1, 3, 4, 6, 2, 5, 3 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Increase to Grade 3;n=1, 2, 3, 2, 4, 1, 3, 2 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Increase to Grade 2;n=1, 2, 3, 2, 4, 1, 3, 2 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Any Grade Increase; n=1, 1, 3, 4, 6, 2, 5, 3 | 3 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Any Grade Increase;n=1, 2, 3, 2, 4, 1, 3, 2 | 2 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Increase to Grade 2;n=1, 1, 3, 4, 6, 2, 5, 3 | 3 Participants |
Primary
Part 1: Number of Participants With Change From Baseline in Temperature
Temperature was measured after resting for 5 minutes in semi-supine position. Data for participants with temperature decreased to \<=35 Celsius, normal or no change, increase to \>=38 Celsius at worst-case post Baseline is reported.
Time frame: Median of 4 weeks of drug exposure
Population: All Treated Subjects Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1:GSK2879552 1mg QD | Part 1: Number of Participants With Change From Baseline in Temperature | Decrease to <=35 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Part 1: Number of Participants With Change From Baseline in Temperature | Increase to >=38 | 0 Participants |
| Part 1:GSK2879552 1mg QD | Part 1: Number of Participants With Change From Baseline in Temperature | Change to Normal or No Change | 1 Participants |
| Part 1: GSK2879552 2mg QD | Part 1: Number of Participants With Change From Baseline in Temperature | Increase to >=38 | 0 Participants |
| Part 1: GSK2879552 2mg QD | Part 1: Number of Participants With Change From Baseline in Temperature | Change to Normal or No Change | 2 Participants |
| Part 1: GSK2879552 2mg QD | Part 1: Number of Participants With Change From Baseline in Temperature | Decrease to <=35 | 0 Participants |
| Part 1: GSK2879552 4mg QD | Part 1: Number of Participants With Change From Baseline in Temperature | Increase to >=38 | 3 Participants |
| Part 1: GSK2879552 4mg QD | Part 1: Number of Participants With Change From Baseline in Temperature | Decrease to <=35 | 1 Participants |
| Part 1: GSK2879552 4mg QD | Part 1: Number of Participants With Change From Baseline in Temperature | Change to Normal or No Change | 4 Participants |
| Part 1: GSK2879552 8mg QD | Part 1: Number of Participants With Change From Baseline in Temperature | Decrease to <=35 | 0 Participants |
| Part 1: GSK2879552 8mg QD | Part 1: Number of Participants With Change From Baseline in Temperature | Change to Normal or No Change | 4 Participants |
| Part 1: GSK2879552 8mg QD | Part 1: Number of Participants With Change From Baseline in Temperature | Increase to >=38 | 1 Participants |
| Part 1: GSK2879552 12mg QD | Part 1: Number of Participants With Change From Baseline in Temperature | Change to Normal or No Change | 5 Participants |
| Part 1: GSK2879552 12mg QD | Part 1: Number of Participants With Change From Baseline in Temperature | Decrease to <=35 | 0 Participants |
| Part 1: GSK2879552 12mg QD | Part 1: Number of Participants With Change From Baseline in Temperature | Increase to >=38 | 1 Participants |
| Part 1: GSK2879552 20mg QD | Part 1: Number of Participants With Change From Baseline in Temperature | Change to Normal or No Change | 4 Participants |
| Part 1: GSK2879552 20mg QD | Part 1: Number of Participants With Change From Baseline in Temperature | Decrease to <=35 | 0 Participants |
| Part 1: GSK2879552 20mg QD | Part 1: Number of Participants With Change From Baseline in Temperature | Increase to >=38 | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Number of Participants With Change From Baseline in Temperature | Change to Normal or No Change | 9 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Number of Participants With Change From Baseline in Temperature | Decrease to <=35 | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Number of Participants With Change From Baseline in Temperature | Increase to >=38 | 1 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Number of Participants With Change From Baseline in Temperature | Decrease to <=35 | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Number of Participants With Change From Baseline in Temperature | Change to Normal or No Change | 6 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Number of Participants With Change From Baseline in Temperature | Increase to >=38 | 0 Participants |
Primary
Part 1: Number of Participants With Dose Limiting Toxicities (DLT)
An event was considered a DLT if it occursed within the first 28 days of treatment, and meets one of the following criteria unless it can be clearly established that the event was unrelated to treatment: hematologic DLT included myelosuppression, Grade \>=3 non-hematologic toxicity that is considered clinically significant and lasts \>72 hours, Grade 2 toxicity that in the judgment of the investigator and GSK Medical Monitor is dose-limiting and treatment delay of \>=42 days due to unresolved toxicity.
Time frame: Median of 4 weeks of drug exposure
Population: All Treated Subjects Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1:GSK2879552 1mg QD | Part 1: Number of Participants With Dose Limiting Toxicities (DLT) | 0 Participants |
| Part 1: GSK2879552 2mg QD | Part 1: Number of Participants With Dose Limiting Toxicities (DLT) | 0 Participants |
| Part 1: GSK2879552 4mg QD | Part 1: Number of Participants With Dose Limiting Toxicities (DLT) | 0 Participants |
| Part 1: GSK2879552 8mg QD | Part 1: Number of Participants With Dose Limiting Toxicities (DLT) | 0 Participants |
| Part 1: GSK2879552 12mg QD | Part 1: Number of Participants With Dose Limiting Toxicities (DLT) | 1 Participants |
| Part 1: GSK2879552 20mg QD | Part 1: Number of Participants With Dose Limiting Toxicities (DLT) | 0 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Number of Participants With Dose Limiting Toxicities (DLT) | 0 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Number of Participants With Dose Limiting Toxicities (DLT) | 0 Participants |
Primary
Part 1: Number of Participants With Withdrawals Due to Toxicities
Participants were monitored from start of the study till the development of toxicity. The data for number of participants withdrawn due to toxicities has been presented.
Time frame: Median of 4 weeks of drug exposure
Population: All Treated Subjects Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1:GSK2879552 1mg QD | Part 1: Number of Participants With Withdrawals Due to Toxicities | 0 Participants |
| Part 1: GSK2879552 2mg QD | Part 1: Number of Participants With Withdrawals Due to Toxicities | 0 Participants |
| Part 1: GSK2879552 4mg QD | Part 1: Number of Participants With Withdrawals Due to Toxicities | 0 Participants |
| Part 1: GSK2879552 8mg QD | Part 1: Number of Participants With Withdrawals Due to Toxicities | 1 Participants |
| Part 1: GSK2879552 12mg QD | Part 1: Number of Participants With Withdrawals Due to Toxicities | 4 Participants |
| Part 1: GSK2879552 20mg QD | Part 1: Number of Participants With Withdrawals Due to Toxicities | 2 Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Number of Participants With Withdrawals Due to Toxicities | 4 Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Number of Participants With Withdrawals Due to Toxicities | 2 Participants |
Primary
Part 2: Objective Response Rate of Participants
Objective response rate defined as the percentage of participants who achievied complete remission (CR), partial remission (PR), CRp (as per CR but platelet count \<100 x 10\^9/L) and morphologic leukemia free state per response criteria. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time frame: Up to 14 months
Population: All Treated Subjects Population. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study
Secondary
Duration of Response: Part 2
This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time frame: Up to 14 months
Population: All Participants. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Secondary
Number of Participants With Abnormal Covariates: Part 2
This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time frame: Up to 14 months
Population: All Participants. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Secondary
Part 1: Accumulation Ratio for GSK2879552
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. Accumulation ratio was determined dividing AUC (0-tau) on Day 15 by AUC (0-tau) on Day 1. The ratio of accumulation of GSK2879552 was estimated by calculating the ratio of the geometric least squares (GLS) means of the AUC(0-tau) between Day 15 and Day 1 for all dose levels and the corresponding 90 percent confidence interval (CI) for each ratio.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15
Population: PK Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1:GSK2879552 1mg QD | Part 1: Accumulation Ratio for GSK2879552 | 1.881 Ratio |
| Part 1: GSK2879552 2mg QD | Part 1: Accumulation Ratio for GSK2879552 | 1.367 Ratio |
| Part 1: GSK2879552 4mg QD | Part 1: Accumulation Ratio for GSK2879552 | 1.319 Ratio |
| Part 1: GSK2879552 8mg QD | Part 1: Accumulation Ratio for GSK2879552 | 1.037 Ratio |
| Part 1: GSK2879552 12mg QD | Part 1: Accumulation Ratio for GSK2879552 | 1.388 Ratio |
| Part 1: GSK2879552 20mg QD | Part 1: Accumulation Ratio for GSK2879552 | 1.750 Ratio |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Accumulation Ratio for GSK2879552 | 1.073 Ratio |
Secondary
Part 1: Apparent Terminal Phase Half-life (t½)
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. NA indicates that data were not available as geometric coefficient of variation could not be calculated for a single participant.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15
Population: PK Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1:GSK2879552 1mg QD | Part 1: Apparent Terminal Phase Half-life (t½) | 34.6647 Hours | — |
| Part 1: GSK2879552 2mg QD | Part 1: Apparent Terminal Phase Half-life (t½) | 29.7715 Hours | Geometric Coefficient of Variation 37.3 |
| Part 1: GSK2879552 4mg QD | Part 1: Apparent Terminal Phase Half-life (t½) | 19.6564 Hours | Geometric Coefficient of Variation 15.9 |
| Part 1: GSK2879552 8mg QD | Part 1: Apparent Terminal Phase Half-life (t½) | 11.2045 Hours | Geometric Coefficient of Variation 26 |
| Part 1: GSK2879552 12mg QD | Part 1: Apparent Terminal Phase Half-life (t½) | 12.4020 Hours | Geometric Coefficient of Variation 26.5 |
| Part 1: GSK2879552 20mg QD | Part 1: Apparent Terminal Phase Half-life (t½) | 15.9502 Hours | Geometric Coefficient of Variation 20.6 |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Apparent Terminal Phase Half-life (t½) | 14.9631 Hours | Geometric Coefficient of Variation 38.9 |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Apparent Terminal Phase Half-life (t½) | 10.5340 Hours | Geometric Coefficient of Variation 47.8 |
Secondary
Part 1: Apparent Terminal Phase Half-life (t½) of ATRA
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15
Population: PK Population. Plasma samples were not quantifiable for ATRA at all end points and hence the PK parameters could not be derived.
Secondary
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and AUC Over the Dosing Interval (0-tau) After Repeated Administration
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. NA indicates that data were not available as geometric coefficient of variation could not be calculated for a single participant.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 15
Population: PK Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1:GSK2879552 1mg QD | Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and AUC Over the Dosing Interval (0-tau) After Repeated Administration | AUC (0-t) | 22.0069 Hour*nanograms per milliliter | — |
| Part 1:GSK2879552 1mg QD | Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and AUC Over the Dosing Interval (0-tau) After Repeated Administration | AUC (0-tau) | 37.6629 Hour*nanograms per milliliter | — |
| Part 1: GSK2879552 2mg QD | Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and AUC Over the Dosing Interval (0-tau) After Repeated Administration | AUC (0-t) | 82.6381 Hour*nanograms per milliliter | Geometric Coefficient of Variation 31.2 |
| Part 1: GSK2879552 2mg QD | Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and AUC Over the Dosing Interval (0-tau) After Repeated Administration | AUC (0-tau) | 82.8980 Hour*nanograms per milliliter | Geometric Coefficient of Variation 31.5 |
| Part 1: GSK2879552 4mg QD | Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and AUC Over the Dosing Interval (0-tau) After Repeated Administration | AUC (0-t) | 221.5336 Hour*nanograms per milliliter | Geometric Coefficient of Variation 48.2 |
| Part 1: GSK2879552 4mg QD | Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and AUC Over the Dosing Interval (0-tau) After Repeated Administration | AUC (0-tau) | 221.6595 Hour*nanograms per milliliter | Geometric Coefficient of Variation 48.2 |
| Part 1: GSK2879552 8mg QD | Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and AUC Over the Dosing Interval (0-tau) After Repeated Administration | AUC (0-t) | 692.8434 Hour*nanograms per milliliter | Geometric Coefficient of Variation 62.3 |
| Part 1: GSK2879552 8mg QD | Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and AUC Over the Dosing Interval (0-tau) After Repeated Administration | AUC (0-tau) | 699.1461 Hour*nanograms per milliliter | Geometric Coefficient of Variation 62.3 |
| Part 1: GSK2879552 12mg QD | Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and AUC Over the Dosing Interval (0-tau) After Repeated Administration | AUC (0-t) | 623.2032 Hour*nanograms per milliliter | Geometric Coefficient of Variation 63.9 |
| Part 1: GSK2879552 12mg QD | Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and AUC Over the Dosing Interval (0-tau) After Repeated Administration | AUC (0-tau) | 661.7915 Hour*nanograms per milliliter | Geometric Coefficient of Variation 58 |
| Part 1: GSK2879552 20mg QD | Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and AUC Over the Dosing Interval (0-tau) After Repeated Administration | AUC (0-t) | 1158.6530 Hour*nanograms per milliliter | Geometric Coefficient of Variation 27.3 |
| Part 1: GSK2879552 20mg QD | Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and AUC Over the Dosing Interval (0-tau) After Repeated Administration | AUC (0-tau) | 1152.0895 Hour*nanograms per milliliter | Geometric Coefficient of Variation 24.9 |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and AUC Over the Dosing Interval (0-tau) After Repeated Administration | AUC (0-tau) | 142.6193 Hour*nanograms per milliliter | Geometric Coefficient of Variation 35 |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and AUC Over the Dosing Interval (0-tau) After Repeated Administration | AUC (0-t) | 132.0625 Hour*nanograms per milliliter | Geometric Coefficient of Variation 38.4 |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and AUC Over the Dosing Interval (0-tau) After Repeated Administration | AUC (0-t) | 904.0276 Hour*nanograms per milliliter | Geometric Coefficient of Variation 30.2 |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and AUC Over the Dosing Interval (0-tau) After Repeated Administration | AUC (0-tau) | 904.2889 Hour*nanograms per milliliter | Geometric Coefficient of Variation 30 |
Secondary
Part 1: Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and From Time Zero (Pre-dose) Extrapolated to Infinite Time [(AUC(0-inf)] After Single Dose Administration
Blood samples were collected at indicated time points. The Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis. NA indicates that data were not available as geometric co-efficient of variation could not be calculated for a single participant.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1
Population: PK Population comprised of all treated participants for whom a PK sample was obtained and analyzed. Only those participants with available data at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1:GSK2879552 1mg QD | Part 1: Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and From Time Zero (Pre-dose) Extrapolated to Infinite Time [(AUC(0-inf)] After Single Dose Administration | AUC(0-t) n=1, 2, 7, 5, 6,4, 9,5 | 30.9457 Hour*nanograms per milliliter | — |
| Part 1:GSK2879552 1mg QD | Part 1: Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and From Time Zero (Pre-dose) Extrapolated to Infinite Time [(AUC(0-inf)] After Single Dose Administration | AUC(0-inf); n=1, 2, 7, 5, 6,4, 8,5 | 36.8470 Hour*nanograms per milliliter | — |
| Part 1: GSK2879552 2mg QD | Part 1: Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and From Time Zero (Pre-dose) Extrapolated to Infinite Time [(AUC(0-inf)] After Single Dose Administration | AUC(0-t) n=1, 2, 7, 5, 6,4, 9,5 | 62.7579 Hour*nanograms per milliliter | Geometric Coefficient of Variation 40.6 |
| Part 1: GSK2879552 2mg QD | Part 1: Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and From Time Zero (Pre-dose) Extrapolated to Infinite Time [(AUC(0-inf)] After Single Dose Administration | AUC(0-inf); n=1, 2, 7, 5, 6,4, 8,5 | 72.7180 Hour*nanograms per milliliter | Geometric Coefficient of Variation 31.4 |
| Part 1: GSK2879552 4mg QD | Part 1: Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and From Time Zero (Pre-dose) Extrapolated to Infinite Time [(AUC(0-inf)] After Single Dose Administration | AUC(0-t) n=1, 2, 7, 5, 6,4, 9,5 | 211.1387 Hour*nanograms per milliliter | Geometric Coefficient of Variation 34.8 |
| Part 1: GSK2879552 4mg QD | Part 1: Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and From Time Zero (Pre-dose) Extrapolated to Infinite Time [(AUC(0-inf)] After Single Dose Administration | AUC(0-inf); n=1, 2, 7, 5, 6,4, 8,5 | 222.0837 Hour*nanograms per milliliter | Geometric Coefficient of Variation 35.1 |
| Part 1: GSK2879552 8mg QD | Part 1: Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and From Time Zero (Pre-dose) Extrapolated to Infinite Time [(AUC(0-inf)] After Single Dose Administration | AUC(0-t) n=1, 2, 7, 5, 6,4, 9,5 | 549.9557 Hour*nanograms per milliliter | Geometric Coefficient of Variation 64.3 |
| Part 1: GSK2879552 8mg QD | Part 1: Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and From Time Zero (Pre-dose) Extrapolated to Infinite Time [(AUC(0-inf)] After Single Dose Administration | AUC(0-inf); n=1, 2, 7, 5, 6,4, 8,5 | 600.6492 Hour*nanograms per milliliter | Geometric Coefficient of Variation 61.9 |
| Part 1: GSK2879552 12mg QD | Part 1: Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and From Time Zero (Pre-dose) Extrapolated to Infinite Time [(AUC(0-inf)] After Single Dose Administration | AUC(0-t) n=1, 2, 7, 5, 6,4, 9,5 | 738.1552 Hour*nanograms per milliliter | Geometric Coefficient of Variation 77.6 |
| Part 1: GSK2879552 12mg QD | Part 1: Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and From Time Zero (Pre-dose) Extrapolated to Infinite Time [(AUC(0-inf)] After Single Dose Administration | AUC(0-inf); n=1, 2, 7, 5, 6,4, 8,5 | 791.2295 Hour*nanograms per milliliter | Geometric Coefficient of Variation 74.1 |
| Part 1: GSK2879552 20mg QD | Part 1: Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and From Time Zero (Pre-dose) Extrapolated to Infinite Time [(AUC(0-inf)] After Single Dose Administration | AUC(0-t) n=1, 2, 7, 5, 6,4, 9,5 | 974.7759 Hour*nanograms per milliliter | Geometric Coefficient of Variation 24.2 |
| Part 1: GSK2879552 20mg QD | Part 1: Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and From Time Zero (Pre-dose) Extrapolated to Infinite Time [(AUC(0-inf)] After Single Dose Administration | AUC(0-inf); n=1, 2, 7, 5, 6,4, 8,5 | 1125.8508 Hour*nanograms per milliliter | Geometric Coefficient of Variation 29.7 |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and From Time Zero (Pre-dose) Extrapolated to Infinite Time [(AUC(0-inf)] After Single Dose Administration | AUC(0-inf); n=1, 2, 7, 5, 6,4, 8,5 | 105.4513 Hour*nanograms per milliliter | Geometric Coefficient of Variation 41.7 |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and From Time Zero (Pre-dose) Extrapolated to Infinite Time [(AUC(0-inf)] After Single Dose Administration | AUC(0-t) n=1, 2, 7, 5, 6,4, 9,5 | 97.6341 Hour*nanograms per milliliter | Geometric Coefficient of Variation 38.8 |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and From Time Zero (Pre-dose) Extrapolated to Infinite Time [(AUC(0-inf)] After Single Dose Administration | AUC(0-t) n=1, 2, 7, 5, 6,4, 9,5 | 968.7825 Hour*nanograms per milliliter | Geometric Coefficient of Variation 36.1 |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and From Time Zero (Pre-dose) Extrapolated to Infinite Time [(AUC(0-inf)] After Single Dose Administration | AUC(0-inf); n=1, 2, 7, 5, 6,4, 8,5 | 1101.4318 Hour*nanograms per milliliter | Geometric Coefficient of Variation 41 |
Secondary
Part 1: AUC(0-t), AUC (0-tau) and AUC(0-inf) of ATRA
Blood samples were collected at indicated time points. The Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1and Day 15
Population: PK Population. Plasma samples were not quantifiable for ATRA at all end points and hence the PK parameters could not be derived.
Secondary
Part 1: AUC Over the Dosing Interval (0-tau) After Single Dose Administration
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. NA indicates that data were not available as geometric co-efficient could not be calculated for a single participant.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1
Population: PK Population. Only those participants with available data at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1:GSK2879552 1mg QD | Part 1: AUC Over the Dosing Interval (0-tau) After Single Dose Administration | 22.2630 Hour*nanograms per milliliter | — |
| Part 1: GSK2879552 2mg QD | Part 1: AUC Over the Dosing Interval (0-tau) After Single Dose Administration | 44.0692 Hour*nanograms per milliliter | Geometric Coefficient of Variation 45.5 |
| Part 1: GSK2879552 4mg QD | Part 1: AUC Over the Dosing Interval (0-tau) After Single Dose Administration | 169.5072 Hour*nanograms per milliliter | Geometric Coefficient of Variation 35.1 |
| Part 1: GSK2879552 8mg QD | Part 1: AUC Over the Dosing Interval (0-tau) After Single Dose Administration | 483.7209 Hour*nanograms per milliliter | Geometric Coefficient of Variation 62.2 |
| Part 1: GSK2879552 12mg QD | Part 1: AUC Over the Dosing Interval (0-tau) After Single Dose Administration | 638.4389 Hour*nanograms per milliliter | Geometric Coefficient of Variation 70.3 |
| Part 1: GSK2879552 20mg QD | Part 1: AUC Over the Dosing Interval (0-tau) After Single Dose Administration | 870.8045 Hour*nanograms per milliliter | Geometric Coefficient of Variation 21 |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: AUC Over the Dosing Interval (0-tau) After Single Dose Administration | 80.2478 Hour*nanograms per milliliter | Geometric Coefficient of Variation 48.4 |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: AUC Over the Dosing Interval (0-tau) After Single Dose Administration | 885.8174 Hour*nanograms per milliliter | Geometric Coefficient of Variation 24.1 |
Secondary
Part 1: Cmax of ATRA
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15
Population: PK Population. Plasma samples were not quantifiable for ATRA at all end points and hence the PK parameters could not be derived.
Secondary
Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK2879552
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. NA indicates that data were not available as geometric coefficient of variation could not be calculated for a single participant.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15
Population: PK Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1:GSK2879552 1mg QD | Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK2879552 | Day 1,n=1,2,7,5,6,4,9,5 | 4.0660 Nanograms per milliliter | — |
| Part 1:GSK2879552 1mg QD | Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK2879552 | Day 15,n=1,2,4,4,6,2,6,4 | 4.3920 Nanograms per milliliter | — |
| Part 1: GSK2879552 2mg QD | Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK2879552 | Day 1,n=1,2,7,5,6,4,9,5 | 7.5501 Nanograms per milliliter | Geometric Coefficient of Variation 34.2 |
| Part 1: GSK2879552 2mg QD | Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK2879552 | Day 15,n=1,2,4,4,6,2,6,4 | 11.5411 Nanograms per milliliter | Geometric Coefficient of Variation 60.1 |
| Part 1: GSK2879552 4mg QD | Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK2879552 | Day 1,n=1,2,7,5,6,4,9,5 | 28.5460 Nanograms per milliliter | Geometric Coefficient of Variation 32 |
| Part 1: GSK2879552 4mg QD | Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK2879552 | Day 15,n=1,2,4,4,6,2,6,4 | 40.1989 Nanograms per milliliter | Geometric Coefficient of Variation 52 |
| Part 1: GSK2879552 8mg QD | Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK2879552 | Day 1,n=1,2,7,5,6,4,9,5 | 65.5650 Nanograms per milliliter | Geometric Coefficient of Variation 59.8 |
| Part 1: GSK2879552 8mg QD | Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK2879552 | Day 15,n=1,2,4,4,6,2,6,4 | 83.2978 Nanograms per milliliter | Geometric Coefficient of Variation 32.9 |
| Part 1: GSK2879552 12mg QD | Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK2879552 | Day 1,n=1,2,7,5,6,4,9,5 | 98.6033 Nanograms per milliliter | Geometric Coefficient of Variation 73.1 |
| Part 1: GSK2879552 12mg QD | Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK2879552 | Day 15,n=1,2,4,4,6,2,6,4 | 103.0141 Nanograms per milliliter | Geometric Coefficient of Variation 65.7 |
| Part 1: GSK2879552 20mg QD | Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK2879552 | Day 1,n=1,2,7,5,6,4,9,5 | 134.8388 Nanograms per milliliter | Geometric Coefficient of Variation 12.8 |
| Part 1: GSK2879552 20mg QD | Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK2879552 | Day 15,n=1,2,4,4,6,2,6,4 | 224.2444 Nanograms per milliliter | Geometric Coefficient of Variation 17.7 |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK2879552 | Day 15,n=1,2,4,4,6,2,6,4 | 16.7684 Nanograms per milliliter | Geometric Coefficient of Variation 37 |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK2879552 | Day 1,n=1,2,7,5,6,4,9,5 | 13.3889 Nanograms per milliliter | Geometric Coefficient of Variation 63.3 |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK2879552 | Day 1,n=1,2,7,5,6,4,9,5 | 142.8826 Nanograms per milliliter | Geometric Coefficient of Variation 28.6 |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK2879552 | Day 15,n=1,2,4,4,6,2,6,4 | 144.6871 Nanograms per milliliter | Geometric Coefficient of Variation 25.4 |
Secondary
Part 1:Percentage of Participants With Objective Response
Objective response rate is defined as the percentage of participants who achieved CR, PR, as per CR but platelet count \<100 x 10\^9/L and morphologic leukemia free state per response criteria.
Time frame: Median of 4 weeks drug response
Population: All Treated Subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1:GSK2879552 1mg QD | Part 1:Percentage of Participants With Objective Response | 0 Percentage of Participants |
| Part 1: GSK2879552 2mg QD | Part 1:Percentage of Participants With Objective Response | 0 Percentage of Participants |
| Part 1: GSK2879552 4mg QD | Part 1:Percentage of Participants With Objective Response | 0 Percentage of Participants |
| Part 1: GSK2879552 8mg QD | Part 1:Percentage of Participants With Objective Response | 0 Percentage of Participants |
| Part 1: GSK2879552 12mg QD | Part 1:Percentage of Participants With Objective Response | 17 Percentage of Participants |
| Part 1: GSK2879552 20mg QD | Part 1:Percentage of Participants With Objective Response | 0 Percentage of Participants |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1:Percentage of Participants With Objective Response | 10 Percentage of Participants |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1:Percentage of Participants With Objective Response | 0 Percentage of Participants |
Secondary
Part 1:Time Invariance
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. The time invariance of GSK2879552 was estimated by calculating the ratio of the GLS means of the AUC (0-tau) between Day 15 and Day 1 for all dose levels and the corresponding 90 percent CI for each ratio.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15
Population: PK Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: GSK2879552 2mg QD | Part 1:Time Invariance | 1.140 Ratio |
| Part 1: GSK2879552 4mg QD | Part 1:Time Invariance | 1.030 Ratio |
| Part 1: GSK2879552 8mg QD | Part 1:Time Invariance | 1.042 Ratio |
| Part 1: GSK2879552 12mg QD | Part 1:Time Invariance | 0.836 Ratio |
| Part 1: GSK2879552 20mg QD | Part 1:Time Invariance | 1.167 Ratio |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1:Time Invariance | 1.346 Ratio |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1:Time Invariance | 0.845 Ratio |
Secondary
Part 1: Time of Occurrence of Cmax (Tmax) of ATRA
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15
Population: PK Population. Plasma samples were not quantifiable for ATRA at all end points and hence the PK parameters could not be derived.
Secondary
Part 1: Time of Occurrence of Cmax (Tmax) of GSK2879552
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. NA indicates that data were not available as standard deviation could not be calculated for a single participant.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 1 and 15
Population: PK Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1:GSK2879552 1mg QD | Part 1: Time of Occurrence of Cmax (Tmax) of GSK2879552 | Day 15, n= 1, 2, 4, 4, 6, 2, 6, 4 | 1.0000 Hours |
| Part 1:GSK2879552 1mg QD | Part 1: Time of Occurrence of Cmax (Tmax) of GSK2879552 | Day 1, n=1, 2, 7, 5, 6, 4, 9, 5 | 0.983 Hours |
| Part 1: GSK2879552 2mg QD | Part 1: Time of Occurrence of Cmax (Tmax) of GSK2879552 | Day 1, n=1, 2, 7, 5, 6, 4, 9, 5 | 0.7500 Hours |
| Part 1: GSK2879552 2mg QD | Part 1: Time of Occurrence of Cmax (Tmax) of GSK2879552 | Day 15, n= 1, 2, 4, 4, 6, 2, 6, 4 | 1.0000 Hours |
| Part 1: GSK2879552 4mg QD | Part 1: Time of Occurrence of Cmax (Tmax) of GSK2879552 | Day 1, n=1, 2, 7, 5, 6, 4, 9, 5 | 1.0000 Hours |
| Part 1: GSK2879552 4mg QD | Part 1: Time of Occurrence of Cmax (Tmax) of GSK2879552 | Day 15, n= 1, 2, 4, 4, 6, 2, 6, 4 | 0.7833 Hours |
| Part 1: GSK2879552 8mg QD | Part 1: Time of Occurrence of Cmax (Tmax) of GSK2879552 | Day 15, n= 1, 2, 4, 4, 6, 2, 6, 4 | 1.5833 Hours |
| Part 1: GSK2879552 8mg QD | Part 1: Time of Occurrence of Cmax (Tmax) of GSK2879552 | Day 1, n=1, 2, 7, 5, 6, 4, 9, 5 | 0.9667 Hours |
| Part 1: GSK2879552 12mg QD | Part 1: Time of Occurrence of Cmax (Tmax) of GSK2879552 | Day 1, n=1, 2, 7, 5, 6, 4, 9, 5 | 1.2750 Hours |
| Part 1: GSK2879552 12mg QD | Part 1: Time of Occurrence of Cmax (Tmax) of GSK2879552 | Day 15, n= 1, 2, 4, 4, 6, 2, 6, 4 | 0.8167 Hours |
| Part 1: GSK2879552 20mg QD | Part 1: Time of Occurrence of Cmax (Tmax) of GSK2879552 | Day 15, n= 1, 2, 4, 4, 6, 2, 6, 4 | 0.3833 Hours |
| Part 1: GSK2879552 20mg QD | Part 1: Time of Occurrence of Cmax (Tmax) of GSK2879552 | Day 1, n=1, 2, 7, 5, 6, 4, 9, 5 | 0.6667 Hours |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Time of Occurrence of Cmax (Tmax) of GSK2879552 | Day 1, n=1, 2, 7, 5, 6, 4, 9, 5 | 1.0000 Hours |
| Part 1: GSK2879552 2mg QD/ATRA 45mg/m^2/Day | Part 1: Time of Occurrence of Cmax (Tmax) of GSK2879552 | Day 15, n= 1, 2, 4, 4, 6, 2, 6, 4 | 0.9917 Hours |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Time of Occurrence of Cmax (Tmax) of GSK2879552 | Day 15, n= 1, 2, 4, 4, 6, 2, 6, 4 | 1.3000 Hours |
| Part 1: GSK2879552 20mg QD PK/PD Expansion | Part 1: Time of Occurrence of Cmax (Tmax) of GSK2879552 | Day 1, n=1, 2, 7, 5, 6, 4, 9, 5 | 1.0000 Hours |
Secondary
Part 2: Clearance (CL) of GSK2879552 for Part 2
This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time frame: Day 1 (pre-dose, 0.5 and 3 hours post dose), Days 4, 8 (pre-dose), Day 15 (pre-dose, 0.5, 1, 4, 6 hours), Weeks 4, 5, 6, 7, 8 and every 4 weeks up to Week 48
Population: PK Population. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Secondary
Part 2: Number of Participants With Abnormal Clinical Chemistry Parameters
Data was not collected for Part 2 as the study was terminated early during Part 1.
Time frame: Up to 14 months
Population: All Treated Subjects Population. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Secondary
Part 2: Number of Participants With Abnormal Electrocardiogram (ECG) Findings
This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time frame: Up to 14 months
Population: All Treated Subjects Population. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Secondary
Part 2: Number of Participants With Abnormal Hematology Parameters
Data was not collected for Part 2 as the study was terminated early during Part 1.
Time frame: Up to 14 months
Population: All Treated Subjects Population. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Secondary
Part 2: Number of Participants With Abnormal Physical Examinations
This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time frame: Up to 14 months
Population: All Treated Subjects Population. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Secondary
Part 2: Number of Participants With Abnormal Vital Signs
Data was not collected for Part 2 as the study was terminated early during Part 1.
Time frame: Up to 14 months
Population: All Treated Subjects Population. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Secondary
Part 2: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
An AE is any untoward medical occurrence in a 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, 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.
Time frame: Up to 14 months
Population: All Treated Subjects Population. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Secondary
Part 2: Number of Participants With AE Leading to Dose Reductions or Delays
The number of participants who had any dose reduction or delay have been presented. All dose reductions were due to AEs. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time frame: Up to 14 months
Population: All Treated Subjects Population. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Secondary
Part 2: Number of Participants With Withdrawals Due to Toxicities
Participants were monitored from start of the study till the development of toxicity. The data for number of participants withdrawn due to toxicities has been presented. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time frame: Up to 14 months
Population: All Treated Subjects Population. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Secondary
Part 2: Volume of Distribution of GSK2879552 for Part 2
This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time frame: Day 1 (pre-dose, 0.5 and 3 hours post dose), Days 4, 8 (pre-dose), Day 15 (pre-dose, 0.5, 1, 4, 6 hours), Weeks 4, 5, 6, 7, 8 and every 4 weeks up to Week 48
Population: PK Population. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Secondary
Progression-free Survival: Part 2
This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time frame: Up to 14 months
Population: All Participants. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.
Secondary
Time to Time to Response: Part 2
This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time frame: Up to 14 months
Population: All Participants. Data for this endpoint was not collected as this study was terminated early during Part 1 as the risk benefit in relapsed/refractory AML did not favor continuation of the study.