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.
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.
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.
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 The data for number of participants withdrawn due to toxicities has been presented.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Part 1: Number of Participants With Abnormal Physical Examinations
Data for participants with abnormal physical examinations parameters was planned to be recorded.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Part 1: Cmax of ATRA
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
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
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)
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 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.
Progression-free Survival: Part 2
This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.