Safety, Clinical Activity, Pharmacokinetics (PK) and Pharmacodynamics Study of GSK2879552, Alone or With Azacitidine, in Subjects With High Risk Myelodysplastic Syndromes (MDS)

A Phase I/II, Open-label, 2 Arm Study to Investigate the Safety, Clinical Activity, Pharmacokinetics and Pharmacodynamics of GSK2879552 Administered Alone or in Combination With Azacitidine, in Adult Subjects With IPSS-R High and Very High Risk Myelodysplastic Syndromes (MDS) Previously Treated With Hypomethylating Agents (HMA)

Status

Terminated

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02929498

Enrollment

Registered

2016-10-11

Start date

2017-07-31

Completion date

2018-01-31

Last updated

2019-05-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Myelodysplastic Syndrome, Myelodysplastic Syndromes

Keywords

GSK2879552, Revised International Prognostic Scoring System (IPSS-R), azacitidine, hypomethylating agents, myelodysplastic syndrome

Brief summary

This is a Phase I/II, open-label, 2 arm study to evaluate the safety and clinical activity of GSK2879552 alone, or in combination with azacitidine in subjects with MDS. The study consisted of 2 parts. The objective of Part 1 is to determine the recommended phase 2 dose (RP2D) of GSK2879552 administered alone and in combination with azacitidine in adult subjects with high risk MDS previously treated with HMA. The objective of Part 2 is to evaluate clinical activity after treatment with GSK2879552, alone or in combination with azacitidine, in adult subjects with high risk MDS previously treated with HMA.

Interventions

DRUGGSK2879552

GSK2879552 will be administered orally as continuous daily dosing.

DRUGAzacitidine

Azacitidine will be administered at 75 mg/m2 from Day 1 to Day 7 of each 28 day cycle by intravenous (iv) infusion or subcutaneous (sc) injection.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* \>=18 years of age and provided signed written informed consent * Subjects must have IPSS-R high or very high risk myelodysplastic syndromes (MDS) by World Health Organization (WHO) classification * Subjects must have failed hypomethylating treatment where failure is defined as: Progression (according to 2006 International Working Group \[IWG\] criteria) at any time after initiation of the hypomethylating treatment OR Failure to achieve complete or partial response or hematological improvement (HI) (according to 2006 IWG) after at least 4 cycles treatment OR Relapse after initial complete or partial response or HI (according to 2006 IWG criteria). * Subjects are not a candidate, or have failed allogeneic stem cell transplantation. Subjects who underwent allo-transplant in the past are eligible under following conditions: transplant was \>2 year prior to enrolment, and no evidence of active graft-versus-host disease (GVHD) * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. * Subjects must have a life expectancy of at least 12 weeks, in the opinion of the investigator. * 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 defined by: International Normalization Ratio (INR) and activated partial thromboplastin time (aPTT) \<=1.3xupper limit of normal (ULN); platelet count (PLT) \>=10,000 (transfusions permitted to bring PLT to \>10,000); total bilirubin \<=1.5xULN (Isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35% or subject has a diagnosis of Gilbert's syndrome); Alanine transaminase (ALT) \<=2.5xULN; creatinine \<=1.5xULN OR calculated creatinine clearance by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation or measured from 24 hour urine \>=50 milliliters (mL)/minute (min); and Ejection fraction \>=lower limit of normal (LLN) by Echocardiogram (ECHO) or multigated acquisition scan (MUGA) * 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 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

* AML according to world health organization (WHO) criteria (i.e. bone marrow blasts \>20%) * Active hepatitis B or hepatitis C treatment * Baseline Montreal Cognitive Assessment (MOCA) score of 22 or lower * History of or concurrent malignancy of solid tumours, except for below: Exception: Subjects who have been disease-free for 2 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. * Prior treatment with temozolomide, dacarbazine or procarbazine * Prior treatment with poly adenosine diphosphate (ADP) ribose polymerase (PARP) inhibitors (example (e.g.), olaparib, veliparib \[ABT-888\]) * Currently receiving other anti-cancer therapy (chemotherapy, radiation therapy, immuno- therapy, biologic therapy, hormonal therapy, surgery, and/or tumour embolization) * Received major surgery, radiotherapy, or immunotherapy within 4 weeks of GSK2879552 administration * Evidence of severe or uncontrolled systemic diseases (e.g., severe/chronic infection, unstable or uncompensated respiratory, renal, or cardiac disease). Any serious and/or unstable pre-existing medical (aside from malignancy exception above), 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 (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator's assessment) * Patients with any major bleeding current or within the past 4 weeks. (e.g. recent gastrointestinal \[GI\] hemorrhage or neurosurgery). * Administration of an investigational drug within 14 days or 5 half-lives, whichever is shorter, preceding the first dose of study treatment(s) in this study. * Cardiac abnormalities as evidenced by any of the following: clinically significant uncontrolled arrhythmias or uncontrolled hypertension; history or evidence of current \>=Class II congestive heart failure as defined by New York Heart Association (NYHA); history of acute coronary syndromes (including unstable angina and myocardial infarction), coronary angioplasty, or stenting within the past 3 months; baseline Corrected QT (QTc) interval using Fridericia's formula \>450 milliseconds (msec) or \>480 msec in subjects with Bundle Branch Block. QTc value based on single or average of triplicate ECGs obtained over a brief recording period * 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 * 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 * Lactating female * Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GSK2879552 or lysine-specific demethylase 1 (LSD1) inhibitors that contraindicates their participation * Known hypersensitivity to azacitidine or mannitol

Design outcomes

Primary

Measure	Time frame	Description
Part 1: Number of Participants With Any Non-serious Adverse Event (Non-SAE), Serious AE (SAE), Dose Limiting Toxicities (DLT), Dose Reductions or Delays and Withdrawals Due to Toxicities	Up to 2 years	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. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or event associated with liver injury and impaired liver function were categorized as SAE. An event was considered a DLT if it occurred within the first 28 days of treatment, and met the DLT criteria unless it could be clearly established that the event was unrelated to treatment.
Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)	Blood samples were collected from participants for evaluation of hematology parameters including platelets, neutrophils, monocytes, lymphocytes, leucocyte, eosinophils and basophils. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Part 1: Change From Baseline in Mean Corpuscular Volume (MCV) at Indicated Time-points	Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)	Blood samples were collected from participants for evaluation of hematology parameters including MCV. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Part 1: Change From Baseline in Mean Corpuscular Hemoglobin (MCH) at Indicated Time-points	Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)	Blood samples were collected from participants for evaluation of hematology parameters including MCH. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Part 1: Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points	Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)	Blood samples were collected from participants for evaluation of hematology parameters including MCHC and Hb. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Part 1: Change From Baseline in Hematocrit at Indicated Time-points	Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)	Blood samples were collected from participants for evaluation of hematology parameters including Hematocrit. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Part 1: Change From Baseline in Erythrocytes at Indicated Time-points	Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)	Blood samples were collected from participants for evaluation of hematology parameters including erythrocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Part 1: Change From Baseline in Percent Reticulocytes at Indicated Time-points	Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1) (each cycle of 28 days)	Blood samples were collected from participants for evaluation of hematology parameters including percent reticulocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Part 1: Change From Baseline in Blast/Leukocytes at Indicated Time-points	Baseline and Day 1 of Cycle 1 (Cycle of 28 days)	Blood samples were collected from participants for evaluation of hematology parameters including blast/leukocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)	Blood samples were collected from participants for evaluation of clinical chemistry parameters including ALT, ALP, AST, LDH and GGT. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)	Blood samples were collected from participants for evaluation of clinical chemistry parameters including calcium, chloride, glucose, potassium, sodium, phosphate and urea nitrogen. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Part 1: Change From Baseline in Albumin and Protein at Indicated Time Points	Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)	Blood samples were collected from participants for evaluation of clinical chemistry parameters including Albumin and Protein. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Part 1: Change From Baseline in Partial Pressure Carbon Dioxide (pCO2) at Indicated Time Points	Baseline and Day 1 of Cycle 1 (cycle of 28 days)	Blood samples were collected from participants for evaluation of clinical chemistry parameters including pCO2. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time-points	Baseline and Cycle 1 (Days 7, 15), Cycle 2 (Day 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)	Vital signs including SBP and DBP were measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Part 1: Change From Baseline in Heart Rate at Indicated Time-points	Baseline and Cycle 1 (Days 7, 15), Cycle 2 (Day 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)	Vital signs including heart rate was measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Part 1: Change From Baseline in Respiratory Rate at Indicated Time-points	Baseline and Cycle 1 (Days 7, 15), Cycle 2 (Day 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)	Vital signs including respiratory rate was measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Part 1: Change From Baseline in Body Temperature at Indicated Time-points	Baseline and Cycle 1 (Days 7, 15), Cycle 2 (Day 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)	Vital signs including body temperature was measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Part 1: Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate at Indicated Time-points	Baseline and Cycle 1 (Days 1, 7), Cycle 2 (Day 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)	Single 12-lead ECG was obtained at designated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT (QTc) intervals. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points	Baseline and Cycle 1 (Days 1,7), Cycle 2 (Day 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)	Single 12-lead ECG was obtained at designated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Part 1: Number of Participants With Abnormal Findings During Physical Examination	Up to 2 years	A complete physical examination included, at a minimum, assessment of the Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. A brief physical examination included, at a minimum assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). This analysis was planned but data was not captured in the database. Abnormal changes were captured as adverse events if they were clinically significant.
Part 2: Percentage of Participants With Investigator-assessed Best Response Assessed by Clinical Benefit Rate (CBR)	Up to 2.5 years	CBR was defined as the percentage of participants achieving a confirmed Complete Remission (CR) or Partial Remission (PR) or Marrow Complete Remission (mCR) or confirmed Hematologic Improvement (HI) or Stable Disease (SD) prior to new anti-cancer therapy and crossover on the All Treated Subjects Population. Participants with Not Evaluable or missing response were to be treated as non-responders. International Working Group (IWG) criteria, 2006 was to be used to evaluate response.
Part 2: Percentage of Participants With Investigator-assessed Best Response Assessed by Objective Response Rate (ORR)	Up to 2.5 years	Objective response rate was defined as the percentage of participants who achieved CR or PR or mCR or HI prior to new anti-cancer therapy on the All Treated Subjects Population. Participants with Not Evaluable or missing response were to be treated as non-responders. IWG criteria, 2006 was to be used to evaluate response.
Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points	Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)	Blood samples were collected from participants for evaluation of clinical chemistry parameters including Total Bilirubin, Direct Bilirubin, Creatinine and urate. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Secondary

Measure	Time frame	Description
Part 2: Change From Baseline in pCO2 at Indicated Time Points	Baseline and up to 2.5 years	Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including pCO2. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Part 2: Change From Baseline in SBP and DBP at Indicated Time-points	Baseline and up to 2.5 years	Vital signs including SBP and DBP were to be measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Part 2: Change From Baseline in Heart Rate at Indicated Time-points	Baseline and up to 2.5 years	Vital signs including heart rate was to be measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Part 2: Change From Baseline in Respiratory Rate at Indicated Time-points	Baseline and up to 2.5 years	Vital signs including respiratory rate was to be measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Part 2: Change From Baseline in Body Temperature at Indicated Time-points	Baseline and up to 2.5 years	Vital signs including body temperature was to be measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Part 2: Change From Baseline in ECG Mean Heart Rate at Indicated Time-points	Baseline and up to 2.5 years	Single 12-lead ECG was to be obtained at designated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Part 2: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time-points	Baseline and up to 2.5 years	Single 12-lead ECG was to be obtained at designated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Part 2: Number of Participants With Abnormal Findings During Physical Examination	Up to 2.5 years	A complete physical examination included, at a minimum, assessment of the Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. A brief physical examination included, at a minimum assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen).
Part 2: Plasma Clearance (CL/F) of GSK2879552	Cycle 1, Day 1: pre-dose, 0.5, 1, 3 hour; pre-dose on Day 4; Day 7: pre-dose, 0.5, 1, 3 hour; Day 15: pre-dose, 0.5-1 hour post-dose; pre-dose on Day 22; Cycle 2: pre-dose on Days 1, 7, 15, 22; Pre-dose on Day 1 of Cycles 3 to 1 (each cycle of 28 days)	Blood samples were to be collected at indicated time points to evaluate CL/F of GSK2879552. Each PK sample was to be collected as close as possible to the planned time relative to the dose (i.e., time zero) administered to the participant on PK days.
Part 2: Duration of Response	Up to 2.5 years	Duration of response is defined as the time from first documented evidence of response until the first documented sign of disease progression or death. If no disease progression or death, the duration of response was to be censored at last disease assessment.
Part 2: Progression-free Survival	Up to 2.5 years	Progression-free survival is defined as the time from first treatment dose until the first documented sign of disease progression or death. If the participant missed more than one visit prior to the date of documented events, PFS was to be censored at the last adequate assessment prior to missing. Otherwise, if the participant did not have a documented date of events, PFS was to be censored at the date of the last adequate assessment.
Part 2: Overall Survival	Up to 2.5 years	Overall survival is defined as the time from first treatment dose until death due to any reason. For the analysis of overall survival, the last date of known contact was to be used for those participants who had not died at the time of analysis; such participants were to be considered censored.
Part 2: Percentage of Participants With Disease Progression to AML	Up to 2.5 years	The percentage of participants experiencing AML on the All Treated Subjects Population was to be presented.
Part 2: Time to AML Progression	Up to 2.5 years	Time to AML progression is defined as the time from first treatment dose until AML progression or crossover if using the All Treated Subjects Population. For the analysis of time to AML, if the participant did not experience AML, time to AML was to be censored at the last treatment prior to the initiation of anti-cancer therapy or crossover.
Part 1: Percentage of Participants With Investigator-assessed Best Response Assessed by Clinical Benefit Rate (CBR)	Up to 2 years	Clinical Benefit Rate was defined as the percentage of participants achieving a confirmed Complete Remission (CR) or Partial Remission (PR) or Marrow Complete Remission (mCR) or confirmed Hematologic Improvement (HI) or Stable Disease (SD) prior to new anti-cancer therapy and crossover on the All Treated Subjects Population. Participants with Not Evaluable or missing response were treated as non-responders. International Working Group (IWG) criteria, 2006 was used to evaluate response.
Part 2: Number of Participants With Documented Platelet and Red Blood Cell (RBC) Transfusions Per Month	Up to 2.5 years	Number of participants with documented platelet and RBC transfusions were to be presented.
Part 1: Percentage of Participants With Investigator-assessed Best Response Assessed by Objective Response Rate (ORR)	Up to 2 years	Objective Response Rate was defined as the percentage of participants who achieved Complete Remission (CR) or Partial Remission (PR) or Marrow Complete Remission (mCR) or confirmed Hematologic Improvement (HI) prior to new anti-cancer therapy on the All Treated Subjects Population. Participants with Not Evaluable or missing response were treated as non-responders. International Working Group (IWG) criteria, 2006 was used to evaluate response.
Part 1: Plasma Concentration of GSK2879552	Cycle 1, Day 1: pre-dose, 0.5, 1, 3 hour; pre-dose on Days 2,4; Day 7: pre-dose, 0.5, 1, 3 hour; Day 15: pre-dose, 0.5-1 hour post-dose; pre-dose on Day 22; Cycle 2: pre-dose on Days 1, 7, 15, 22; Pre-dose on Day 1 of Cycles 3,4,5 (each cycle of 28 days)	Blood samples were collected at indicated time points to evaluate concentration of GSK2879552. Each Pharmacokinetic (PK) sample was collected as close as possible to the planned time relative to the dose (i.e., time zero) administered to the participant on PK days. PK Concentration Population consisted of all participants in the All Treated Subject Population for whom a blood sample for pharmacokinetics was obtained and analyzed.
Part 1: Plasma Concentration of Azacitidine	Cycle 1, Day 1: pre-dose, 0.5, 1, 3 hour; pre-dose on Days 2,4; Day 7: pre-dose, 0.5, 1, 3 hour; Day 15: pre-dose, 0.5-1 hour post-dose; pre-dose on Day 22; Cycle 2: pre-dose on Days 1, 7, 15, 22; Pre-dose on Day 1 of Cycles 3,4,5 (each cycle of 28 days)	Blood samples were to be collected at indicated time points to evaluate concentration of Azacitidine.
Part 1: Duration of Response	Up to 2 years	Duration of response is defined as the subset of participants (responders) who show a response (CR, mCR, PR, or HI), the time from first documented evidence of response until the first documented sign of disease progression or death. If no disease progression or death, the DOR was to be censored at last disease assessment.
Part 1: Progression-free Survival	Up to 2 years	Progression-free survival (PFS) is defined as the time from first treatment dose until the first documented sign of disease progression or death. If the participant missed more than one visit prior to the date of documented events, PFS was censored at the last adequate assessment prior to missing. Otherwise, if the participant did not have a documented date of events, PFS was censored at the date of the last adequate assessment.
Part 1: Overall Survival	Up to 2 years	Overall survival (OS) is defined as the time from first treatment dose until death due to any reason. For the analysis of overall survival (OS), the last date of known contact was used for those participants who had not died at the time of analysis; such participants were considered censored.
Part 1: Proportion of Participants With Disease Progression to Acute Myeloblastic Leukemia (AML)	Up to 2 years	The proportion of participants with disease progression to AML is defined as the percentage of participants experiencing AML on the All Treated Subjects Population.
Part 1: Time to AML Progression	Up to 2 years	Time to AML progression is defined as the time from first treatment dose until AML progression or crossover if using the All Treated Subjects Population. For the analysis of time to AML, if the participant did not experience AML, time to AML was censored at the last treatment prior to the initiation of anti-cancer therapy or crossover.
Part 1: Number of Participants With Documented Platelet and Red Blood Cell (RBC) Transfusions Per Month	Up to 2 years	Number of participants with documented platelet and RBC transfusions have been presented.
Part 2: Number of Participants With Any AEs and SAEs	Up to 2.5 years	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. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or event associated with liver injury and impaired liver function were categorized as SAE.
Part 2: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Baseline and up to 2.5 years	Blood samples were to be collected from participants for evaluation of hematology parameters including platelets, neutrophils, monocytes, lymphocytes, leucocyte, eosinophils and basophils. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Part 2: Change From Baseline in MCV at Indicated Time-points	Baseline and up to 2.5 years	Blood samples were to be collected from participants for evaluation of hematology parameters including MCV. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Part 2: Change From Baseline in MCH at Indicated Time-points	Baseline and up to 2.5 years	Blood samples were to be collected from participants for evaluation of hematology parameters including MCH. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Part 2: Change From Baseline in MCHC and Hb at Indicated Time-points	Baseline and up to 2.5 years	Blood samples were to be collected from participants for evaluation of hematology parameters including MCHC and Hb. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Part 2: Change From Baseline in Hematocrit at Indicated Time-points	Baseline and up to 2.5 years	Blood samples were to be collected from participants for evaluation of hematology parameters including Hematocrit. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Part 2: Change From Baseline in Erythrocytes at Indicated Time-points	Baseline and up to 2.5 years	Blood samples were to be collected from participants for evaluation of hematology parameters including erythrocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Part 2: Change From Baseline in Percent Reticulocytes at Indicated Time-points	Baseline and up to 2.5 years	Blood samples were to be collected from participants for evaluation of hematology parameters including percent reticulocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Part 2: Change From Baseline in Blast/Leukocytes at Indicated Time-points	Baseline and up to 2.5 years	Blood samples were to be collected from participants for evaluation of hematology parameters including blast/leukocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Part 2: Change From Baseline in ALT, ALP, AST, LDH and GGT at Indicated Time-points	Baseline and up to 2.5 years	Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including ALT, ALP, AST, LDH and GGT. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Part 2: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Baseline and up to 2.5 years	Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including Calcium, chloride, glucose, potassium, sodium, phosphate and urea nitrogen. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Part 2: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points	Baseline and up to 2.5 years	Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including Total Bilirubin, Direct Bilirubin, Creatinine and urate. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Part 2: Change From Baseline in Albumin and Protein at Indicated Time Points	Baseline and up to 2.5 years	Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including Albumin and Protein. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

Countries

Spain, United States

Participant flow

Recruitment details

This was an open-label, 2 arm study to evaluate the safety and clinical activity of GSK2879552 alone, or in combination with azacitidine in adult participants with myelodysplastic syndromes (MDS). The study was conducted in 3 centers among 2 countries.

Pre-assignment details

Total 5 participants were included into Part 1 and received GSK2879552. The study was terminated during Part 1 and hence Part 2 was not conducted as the risk benefit in earlier studies do not favor continuation of this study.

Participants by arm

Arm	Count
Part 1: GSK2879552 Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	5
Part 2: GSK2879552 Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	0
Part 2: GSK2879552+Azacitidine Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter\^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).	0
Total	5

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Part 1: Dose Confirmation (Upto 2 Years)	Death	2	0	0
Part 1: Dose Confirmation (Upto 2 Years)	Study terminated by sponsor	3	0	0

Baseline characteristics

Characteristic	Part 1: GSK2879552	Total	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Age, Continuous	77.2 Years STANDARD_DEVIATION 5.07	77.2 Years STANDARD_DEVIATION 5.07	—	—
Race/Ethnicity, Customized Race White - White/Caucasian/European Heritage	5 Participants	5 Participants	0 Participants	0 Participants
Sex: Female, Male Female	3 Participants	3 Participants	0 Participants	0 Participants
Sex: Female, Male Male	2 Participants	2 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	2 / 5
other Total, other adverse events	5 / 5
serious Total, serious adverse events	1 / 5

Outcome results

Primary

Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points

Blood samples were collected from participants for evaluation of clinical chemistry parameters including ALT, ALP, AST, LDH and GGT. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

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 (MEAN)	Dispersion
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	ALT, Cycle 1, Day 1, n=4	-10.000 International unit per liter (IU/L)	Standard Deviation 18.1292
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	ALT Cycle 1, Day 7, n=5	-3.000 International unit per liter (IU/L)	Standard Deviation 13.5093
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	ALT Cycle 1, Day 15, n=4	-6.250 International unit per liter (IU/L)	Standard Deviation 15.5
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	ALT Cycle 1, Day 22, n=3	1.333 International unit per liter (IU/L)	Standard Deviation 15.1767
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	ALT Cycle 2, Day 1, n=3	3.000 International unit per liter (IU/L)	Standard Deviation 39.5095
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	ALT Cycle 3, Day 1, n=3	3.333 International unit per liter (IU/L)	Standard Deviation 42.004
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	ALT Cycle 4, Day 1, n=2	33.000 International unit per liter (IU/L)	Standard Deviation 1.4142
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	ALT Cycle 5, Day 1, n=1	3.000 International unit per liter (IU/L)	—
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	ALP, Cycle 1, Day 1, n=4	-4.750 International unit per liter (IU/L)	Standard Deviation 3.2016
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	ALP Cycle 1, Day 7, n=5	-6.800 International unit per liter (IU/L)	Standard Deviation 10.3053
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	ALP Cycle 1, Day 15, n=4	-4.250 International unit per liter (IU/L)	Standard Deviation 22.3961
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	ALP Cycle 1, Day 22, n=3	8.000 International unit per liter (IU/L)	Standard Deviation 21.6564
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	ALP Cycle 2, Day 1, n=3	23.667 International unit per liter (IU/L)	Standard Deviation 62.5007
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	ALP Cycle 3, Day 1, n=3	15.667 International unit per liter (IU/L)	Standard Deviation 31.3422
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	ALP Cycle 4, Day 1, n=2	18.500 International unit per liter (IU/L)	Standard Deviation 60.1041
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	ALP Cycle 5, Day 1, n=1	21.000 International unit per liter (IU/L)	—
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	AST, Cycle 1, Day 1, n=4	-6.750 International unit per liter (IU/L)	Standard Deviation 14.8633
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	AST Cycle 1, Day 7, n=5	-3.200 International unit per liter (IU/L)	Standard Deviation 9.3381
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	AST Cycle 1, Day 15, n=4	-3.250 International unit per liter (IU/L)	Standard Deviation 17.6517
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	AST Cycle 1, Day 22, n=3	3.000 International unit per liter (IU/L)	Standard Deviation 27.5136
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	AST Cycle 2, Day 1, n=3	-0.333 International unit per liter (IU/L)	Standard Deviation 30.9246
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	AST Cycle 3, Day 1, n=3	-3.667 International unit per liter (IU/L)	Standard Deviation 38.553
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	AST Cycle 4, Day 1, n=2	22.000 International unit per liter (IU/L)	Standard Deviation 21.2132
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	AST Cycle 5, Day 1, n=1	16.000 International unit per liter (IU/L)	—
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	LDH, Cycle 1, Day 1, n=4	4.000 International unit per liter (IU/L)	Standard Deviation 90.9395
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	LDH Cycle 1, Day 7, n=5	-31.200 International unit per liter (IU/L)	Standard Deviation 47.2515
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	LDH Cycle 1, Day 15, n=3	4.000 International unit per liter (IU/L)	Standard Deviation 22.6053
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	LDH Cycle 1, Day 22, n=3	-12.000 International unit per liter (IU/L)	Standard Deviation 47.571
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	LDH Cycle 2, Day 1, n=3	-18.333 International unit per liter (IU/L)	Standard Deviation 55.4106
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	LDH Cycle 3, Day 1, n=3	-20.667 International unit per liter (IU/L)	Standard Deviation 62.7402
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	LDH Cycle 4, Day 1, n=2	12.500 International unit per liter (IU/L)	Standard Deviation 3.5355
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	LDH Cycle 5, Day 1, n=1	11.000 International unit per liter (IU/L)	—
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	GGT, Cycle 1, Day 1, n=1	-17.000 International unit per liter (IU/L)	—
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	GGT Cycle 1, Day 7, n=2	-7.500 International unit per liter (IU/L)	Standard Deviation 9.1924
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	GGT Cycle 1, Day 22, n=1	0.000 International unit per liter (IU/L)	—
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	GGT Cycle 2, Day 1, n=1	3.000 International unit per liter (IU/L)	—
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	GGT Cycle 3, Day 1, n=1	8.000 International unit per liter (IU/L)	—
Part 2: GSK2879552	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points	GGT Cycle 4, Day 1, n=1	5.000 International unit per liter (IU/L)	—

Primary

Part 1: Change From Baseline in Albumin and Protein at Indicated Time Points

Blood samples were collected from participants for evaluation of clinical chemistry parameters including Albumin and Protein. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

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 (MEAN)	Dispersion
Part 2: GSK2879552	Part 1: Change From Baseline in Albumin and Protein at Indicated Time Points	Albumin, Cycle 1, Day 1, n=4	-1.250 G/L	Standard Deviation 2.2174
Part 2: GSK2879552	Part 1: Change From Baseline in Albumin and Protein at Indicated Time Points	Albumin Cycle 1, Day 7, n=4	-1.250 G/L	Standard Deviation 2.5
Part 2: GSK2879552	Part 1: Change From Baseline in Albumin and Protein at Indicated Time Points	Albumin Cycle 1, Day 15, n=3	-1.667 G/L	Standard Deviation 1.5275
Part 2: GSK2879552	Part 1: Change From Baseline in Albumin and Protein at Indicated Time Points	Albumin Cycle 1, Day 22, n=3	-1.333 G/L	Standard Deviation 0.5774
Part 2: GSK2879552	Part 1: Change From Baseline in Albumin and Protein at Indicated Time Points	Albumin Cycle 2, Day 1, n=3	-1.667 G/L	Standard Deviation 2.0817
Part 2: GSK2879552	Part 1: Change From Baseline in Albumin and Protein at Indicated Time Points	Albumin Cycle 3, Day 1, n=3	-6.000 G/L	Standard Deviation 6.245
Part 2: GSK2879552	Part 1: Change From Baseline in Albumin and Protein at Indicated Time Points	Albumin Cycle 4, Day 1, n=2	0.000 G/L	Standard Deviation 1.4142
Part 2: GSK2879552	Part 1: Change From Baseline in Albumin and Protein at Indicated Time Points	Albumin Cycle 5, Day 1, n=1	1.000 G/L	—
Part 2: GSK2879552	Part 1: Change From Baseline in Albumin and Protein at Indicated Time Points	Protein, Cycle 1, Day 1, n=4	-3.250 G/L	Standard Deviation 3.8622
Part 2: GSK2879552	Part 1: Change From Baseline in Albumin and Protein at Indicated Time Points	Protein Cycle 1, Day 7, n=5	-3.200 G/L	Standard Deviation 4.3243
Part 2: GSK2879552	Part 1: Change From Baseline in Albumin and Protein at Indicated Time Points	Protein Cycle 1, Day 15, n=4	-1.500 G/L	Standard Deviation 4.4347
Part 2: GSK2879552	Part 1: Change From Baseline in Albumin and Protein at Indicated Time Points	Protein Cycle 1, Day 22, n=3	-1.667 G/L	Standard Deviation 1.1547
Part 2: GSK2879552	Part 1: Change From Baseline in Albumin and Protein at Indicated Time Points	Protein Cycle 2, Day 1, n=3	-3.333 G/L	Standard Deviation 5.8595
Part 2: GSK2879552	Part 1: Change From Baseline in Albumin and Protein at Indicated Time Points	Protein Cycle 3, Day 1, n=3	-7.333 G/L	Standard Deviation 6.8069
Part 2: GSK2879552	Part 1: Change From Baseline in Albumin and Protein at Indicated Time Points	Protein Cycle 4, Day 1, n=2	-2.000 G/L	Standard Deviation 2.8284
Part 2: GSK2879552	Part 1: Change From Baseline in Albumin and Protein at Indicated Time Points	Protein Cycle 5, Day 1, n=1	0.000 G/L	—

Primary

Part 1: Change From Baseline in Blast/Leukocytes at Indicated Time-points

Blood samples were collected from participants for evaluation of hematology parameters including blast/leukocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and Day 1 of Cycle 1 (Cycle of 28 days)

Population: All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed.

Arm	Measure	Value (MEAN)
Part 2: GSK2879552	Part 1: Change From Baseline in Blast/Leukocytes at Indicated Time-points	0.000 Ratio of blasts to leukocytes

Primary

Part 1: Change From Baseline in Body Temperature at Indicated Time-points

Vital signs including body temperature was measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and Cycle 1 (Days 7, 15), Cycle 2 (Day 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

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 (MEAN)	Dispersion
Part 2: GSK2879552	Part 1: Change From Baseline in Body Temperature at Indicated Time-points	Cycle 5, Day 1, n=1	-0.20 Celsius	—
Part 2: GSK2879552	Part 1: Change From Baseline in Body Temperature at Indicated Time-points	Cycle 1, Day 7, n=5	0.14 Celsius	Standard Deviation 0.279
Part 2: GSK2879552	Part 1: Change From Baseline in Body Temperature at Indicated Time-points	Cycle 1, Day 15, n=4	0.10 Celsius	Standard Deviation 0.216
Part 2: GSK2879552	Part 1: Change From Baseline in Body Temperature at Indicated Time-points	Cycle 2, Day 1, n=3	0.27 Celsius	Standard Deviation 0.231
Part 2: GSK2879552	Part 1: Change From Baseline in Body Temperature at Indicated Time-points	Cycle 3, Day 1, n=3	0.20 Celsius	Standard Deviation 0.3
Part 2: GSK2879552	Part 1: Change From Baseline in Body Temperature at Indicated Time-points	Cycle 4, Day 1, n=2	0.10 Celsius	Standard Deviation 0.283

Primary

Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points

Blood samples were collected from participants for evaluation of clinical chemistry parameters including calcium, chloride, glucose, potassium, sodium, phosphate and urea nitrogen. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

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 (MEAN)	Dispersion
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Glucose Cycle 1, Day 15, n=4	0.014 Millimoles per liter (mmol/L)	Standard Deviation 0.7971
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Glucose Cycle 1, Day 22, n=3	0.870 Millimoles per liter (mmol/L)	Standard Deviation 0.9309
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Calcium, Cycle 1, Day 1, n=3	-0.008 Millimoles per liter (mmol/L)	Standard Deviation 0.052
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Calcium Cycle 1, Day 7, n=4	-0.075 Millimoles per liter (mmol/L)	Standard Deviation 0.0535
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Calcium Cycle 1, Day 15, n=3	-0.066 Millimoles per liter (mmol/L)	Standard Deviation 0.0758
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Calcium Cycle 1, Day 22, n=3	-0.033 Millimoles per liter (mmol/L)	Standard Deviation 0.0624
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Calcium Cycle 2, Day 1, n=3	-0.067 Millimoles per liter (mmol/L)	Standard Deviation 0.0144
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Calcium Cycle 3, Day 1, n=3	-0.183 Millimoles per liter (mmol/L)	Standard Deviation 0.1523
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Calcium Cycle 4, Day 1, n=2	-0.050 Millimoles per liter (mmol/L)	Standard Deviation 0.07
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Calcium, Cycle 5, Day 1, n=1	-0.050 Millimoles per liter (mmol/L)	—
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Chloride, Cycle 1, Day 1, n=4	-0.750 Millimoles per liter (mmol/L)	Standard Deviation 0.5
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Chloride Cycle 1, Day 7, n=5	0.600 Millimoles per liter (mmol/L)	Standard Deviation 4.3932
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Chloride Cycle 1, Day 15, n=4	0.250 Millimoles per liter (mmol/L)	Standard Deviation 2.5
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Chloride Cycle 1, Day 22, n=3	0.333 Millimoles per liter (mmol/L)	Standard Deviation 1.1547
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Chloride Cycle 2, Day 1, n=3	0.333 Millimoles per liter (mmol/L)	Standard Deviation 1.5275
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Chloride Cycle 3, Day 1, n=3	-0.333 Millimoles per liter (mmol/L)	Standard Deviation 1.5275
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Chloride Cycle 4, Day 1, n=2	0.000 Millimoles per liter (mmol/L)	Standard Deviation 2.8284
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Chloride, Cycle 5, Day 1, n=1	0.000 Millimoles per liter (mmol/L)	—
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Glucose, Cycle 1, Day 1, n=4	0.527 Millimoles per liter (mmol/L)	Standard Deviation 1.9147
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Glucose Cycle 1, Day 7, n=5	-0.333 Millimoles per liter (mmol/L)	Standard Deviation 1.5357
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Glucose Cycle 2, Day 1, n=3	1.924 Millimoles per liter (mmol/L)	Standard Deviation 2.1037
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Glucose Cycle 3, Day 1, n=3	1.628 Millimoles per liter (mmol/L)	Standard Deviation 2.8543
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Glucose Cycle 4, Day 1, n=2	1.027 Millimoles per liter (mmol/L)	Standard Deviation 1.2954
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Glucose, Cycle 5, Day 1, n=1	1.110 Millimoles per liter (mmol/L)	—
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Potassium, Cycle 1, Day 1, n=4	0.325 Millimoles per liter (mmol/L)	Standard Deviation 0.5315
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Potassium Cycle 1, Day 7, n=5	0.000 Millimoles per liter (mmol/L)	Standard Deviation 0.4528
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Potassium Cycle 1, Day 15, n=4	-0.025 Millimoles per liter (mmol/L)	Standard Deviation 0.4272
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Potassium Cycle 1, Day 22, n=3	0.067 Millimoles per liter (mmol/L)	Standard Deviation 0.2887
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Potassium Cycle 2, Day 1, n=3	0.067 Millimoles per liter (mmol/L)	Standard Deviation 0.1528
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Potassium Cycle 3, Day 1, n=3	-0.367 Millimoles per liter (mmol/L)	Standard Deviation 0.3786
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Potassium Cycle 4, Day 1, n=2	0.050 Millimoles per liter (mmol/L)	Standard Deviation 0.0707
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Potassium, Cycle 5, Day 1, n=1	0.500 Millimoles per liter (mmol/L)	—
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Sodium, Cycle 1, Day 1, n=4	-1.750 Millimoles per liter (mmol/L)	Standard Deviation 1.2583
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Sodium Cycle 1, Day 7, n=5	-1.000 Millimoles per liter (mmol/L)	Standard Deviation 2.2361
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Sodium Cycle 1, Day 15, n=4	-2.000 Millimoles per liter (mmol/L)	Standard Deviation 2.4495
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Sodium Cycle 1, Day 22, n=3	-0.667 Millimoles per liter (mmol/L)	Standard Deviation 2.0817
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Sodium Cycle 2, Day 1, n=3	0.333 Millimoles per liter (mmol/L)	Standard Deviation 0.5774
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Sodium Cycle 3, Day 1, n=3	-1.000 Millimoles per liter (mmol/L)	Standard Deviation 5
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Sodium Cycle 4, Day 1, n=2	-0.500 Millimoles per liter (mmol/L)	Standard Deviation 2.1213
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Sodium, Cycle 5, Day 1, n=1	0.000 Millimoles per liter (mmol/L)	—
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Urea nitrogen, Cycle 1, Day 1, n=3	2.701 Millimoles per liter (mmol/L)	Standard Deviation 2.3181
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Urea nitrogen Cycle 1, Day 7, n=4	1.214 Millimoles per liter (mmol/L)	Standard Deviation 3.4779
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Urea nitrogen Cycle 1, Day 15, n=3	1.547 Millimoles per liter (mmol/L)	Standard Deviation 3.3171
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Urea nitrogen Cycle 1, Day 22, n=3	1.309 Millimoles per liter (mmol/L)	Standard Deviation 3.8173
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Urea nitrogen Cycle 2, Day 1, n=3	0.238 Millimoles per liter (mmol/L)	Standard Deviation 2.1519
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Urea nitrogen Cycle 3, Day 1, n=3	-1.190 Millimoles per liter (mmol/L)	Standard Deviation 1.761
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Urea nitrogen Cycle 4, Day 1, n=2	-0.535 Millimoles per liter (mmol/L)	Standard Deviation 1.2622
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Urea nitrogen, Cycle 5, Day 1, n=1	-1.428 Millimoles per liter (mmol/L)	—
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Phosphate, Cycle 1, Day 1, n=1	0.194 Millimoles per liter (mmol/L)	—
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Phosphate Cycle 1, Day 7, n=2	-0.081 Millimoles per liter (mmol/L)	Standard Deviation 0.1598
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Phosphate Cycle 1, Day 22, n=1	-0.032 Millimoles per liter (mmol/L)	—
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Phosphate Cycle 2, Day 1, n=1	0.194 Millimoles per liter (mmol/L)	—
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Phosphate Cycle 3, Day 1, n=1	0.000 Millimoles per liter (mmol/L)	—
Part 2: GSK2879552	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points	Phosphate Cycle 4, Day 1, n=1	0.032 Millimoles per liter (mmol/L)	—

Primary

Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points

Single 12-lead ECG was obtained at designated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and Cycle 1 (Days 1,7), Cycle 2 (Day 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

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 (MEAN)	Dispersion
Part 2: GSK2879552	Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points	PR interval, Cycle 2, Day 1, n=3	6.0 Milliseconds	Standard Deviation 9.17
Part 2: GSK2879552	Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points	PR interval, Cycle 3, Day 1, n=3	0.7 Milliseconds	Standard Deviation 8.08
Part 2: GSK2879552	Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points	QRS duration, Cycle 1, Day 7, n=5	-17.2 Milliseconds	Standard Deviation 39.61
Part 2: GSK2879552	Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points	QTcF interval, Cycle 1, Day 7, n=5	-9.4 Milliseconds	Standard Deviation 38.12
Part 2: GSK2879552	Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points	PR interval, Cycle 1, Day 1, n=2	0.0 Milliseconds	Standard Deviation 0
Part 2: GSK2879552	Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points	PR interval, Cycle 1, Day 7, n=5	39.8 Milliseconds	Standard Deviation 88.34
Part 2: GSK2879552	Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points	PR interval, Cycle 4, Day 1, n=2	6.0 Milliseconds	Standard Deviation 14.14
Part 2: GSK2879552	Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points	PR interval, Cycle 5, Day 1, n=1	12.0 Milliseconds	—
Part 2: GSK2879552	Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points	QRS duration, Cycle 1, Day 1, n=2	-1.0 Milliseconds	Standard Deviation 4.24
Part 2: GSK2879552	Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points	QRS duration, Cycle 2, Day 1, n=3	2.0 Milliseconds	Standard Deviation 2
Part 2: GSK2879552	Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points	QRS duration, Cycle 3, Day 1, n=3	3.3 Milliseconds	Standard Deviation 1.15
Part 2: GSK2879552	Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points	QRS duration, Cycle 4, Day 1, n=2	-1.0 Milliseconds	Standard Deviation 1.41
Part 2: GSK2879552	Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points	QRS duration, Cycle 5, Day 1, n=1	-8.0 Milliseconds	—
Part 2: GSK2879552	Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points	QT interval, Cycle 1, Day 1, n=2	0.0 Milliseconds	Standard Deviation 0
Part 2: GSK2879552	Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points	QT interval, Cycle 1, Day 7, n=5	-5.6 Milliseconds	Standard Deviation 29.37
Part 2: GSK2879552	Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points	QT interval, Cycle 2, Day 1, n=3	24.7 Milliseconds	Standard Deviation 18.58
Part 2: GSK2879552	Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points	QT interval, Cycle 3, Day 1, n=3	2.0 Milliseconds	Standard Deviation 18
Part 2: GSK2879552	Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points	QT interval, Cycle 4, Day 1, n=1	-4.0 Milliseconds	—
Part 2: GSK2879552	Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points	QT interval, Cycle 5, Day 1, n=1	14.0 Milliseconds	—
Part 2: GSK2879552	Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points	QTcB interval, Cycle 1, Day 1, n=2	7.0 Milliseconds	Standard Deviation 9.9
Part 2: GSK2879552	Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points	QTcB interval, Cycle 1, Day 7, n=2	-35.5 Milliseconds	Standard Deviation 82.73
Part 2: GSK2879552	Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points	QTcF interval, Cycle 1, Day 1, n=2	4.5 Milliseconds	Standard Deviation 6.36
Part 2: GSK2879552	Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points	QTcF interval, Cycle 2, Day 1, n=3	8.0 Milliseconds	Standard Deviation 5.57
Part 2: GSK2879552	Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points	QTcF interval, Cycle 3, Day 1, n=3	13.0 Milliseconds	Standard Deviation 18.52
Part 2: GSK2879552	Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points	QTcF interval, Cycle 4, Day 1, n=2	-6.0 Milliseconds	Standard Deviation 19.8
Part 2: GSK2879552	Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points	QTcF interval, Cycle 5, Day 1, n=1	-8.0 Milliseconds	—

Primary

Part 1: Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate at Indicated Time-points

Single 12-lead ECG was obtained at designated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT (QTc) intervals. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and Cycle 1 (Days 1, 7), Cycle 2 (Day 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

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 (MEAN)	Dispersion
Part 2: GSK2879552	Part 1: Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate at Indicated Time-points	Cycle 1, Day 1, n=2	2.0 Beats per minute	Standard Deviation 2.83
Part 2: GSK2879552	Part 1: Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate at Indicated Time-points	Cycle 1, Day 7, n=5	-1.0 Beats per minute	Standard Deviation 11.94
Part 2: GSK2879552	Part 1: Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate at Indicated Time-points	Cycle 2, Day 1, n=3	-5.3 Beats per minute	Standard Deviation 5.51
Part 2: GSK2879552	Part 1: Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate at Indicated Time-points	Cycle 3, Day 1, n=3	2.3 Beats per minute	Standard Deviation 10.02
Part 2: GSK2879552	Part 1: Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate at Indicated Time-points	Cycle 4, Day 1, n=2	-3.0 Beats per minute	Standard Deviation 9.9
Part 2: GSK2879552	Part 1: Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate at Indicated Time-points	Cycle 5, Day 1, n=1	-7.0 Beats per minute	—

Primary

Part 1: Change From Baseline in Erythrocytes at Indicated Time-points

Blood samples were collected from participants for evaluation of hematology parameters including erythrocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

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 (MEAN)	Dispersion
Part 2: GSK2879552	Part 1: Change From Baseline in Erythrocytes at Indicated Time-points	Cycle 1, Day 22, n=3	0.077 10^12 cells per Liter	Standard Deviation 0.0643
Part 2: GSK2879552	Part 1: Change From Baseline in Erythrocytes at Indicated Time-points	Cycle 1, Day 1, n=5	0.030 10^12 cells per Liter	Standard Deviation 0.3489
Part 2: GSK2879552	Part 1: Change From Baseline in Erythrocytes at Indicated Time-points	Cycle 1, Day 7, n=5	-0.058 10^12 cells per Liter	Standard Deviation 0.5363
Part 2: GSK2879552	Part 1: Change From Baseline in Erythrocytes at Indicated Time-points	Cycle 1, Day 15, n=4	-0.138 10^12 cells per Liter	Standard Deviation 0.3216
Part 2: GSK2879552	Part 1: Change From Baseline in Erythrocytes at Indicated Time-points	Cycle 2, Day 1, n=3	-0.193 10^12 cells per Liter	Standard Deviation 0.2558
Part 2: GSK2879552	Part 1: Change From Baseline in Erythrocytes at Indicated Time-points	Cycle 2, Day 7, n=3	-0.017 10^12 cells per Liter	Standard Deviation 0.2996
Part 2: GSK2879552	Part 1: Change From Baseline in Erythrocytes at Indicated Time-points	Cycle 2, Day 15, n=3	-0.063 10^12 cells per Liter	Standard Deviation 0.3402
Part 2: GSK2879552	Part 1: Change From Baseline in Erythrocytes at Indicated Time-points	Cycle 2, Day 22, n=3	-0.173 10^12 cells per Liter	Standard Deviation 0.1901
Part 2: GSK2879552	Part 1: Change From Baseline in Erythrocytes at Indicated Time-points	Cycle 3, Day 1, n=3	-0.160 10^12 cells per Liter	Standard Deviation 0.2425
Part 2: GSK2879552	Part 1: Change From Baseline in Erythrocytes at Indicated Time-points	Cycle 4, Day 1, n=2	0.060 10^12 cells per Liter	Standard Deviation 0.0141
Part 2: GSK2879552	Part 1: Change From Baseline in Erythrocytes at Indicated Time-points	Cycle 5, Day 1, n=1	0.000 10^12 cells per Liter	—

Primary

Part 1: Change From Baseline in Heart Rate at Indicated Time-points

Vital signs including heart rate was measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and Cycle 1 (Days 7, 15), Cycle 2 (Day 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

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 (MEAN)	Dispersion
Part 2: GSK2879552	Part 1: Change From Baseline in Heart Rate at Indicated Time-points	Cycle 1, Day 7, n=5	4.8 Beats per minute	Standard Deviation 6.69
Part 2: GSK2879552	Part 1: Change From Baseline in Heart Rate at Indicated Time-points	Cycle 1, Day 15, n=4	-2.5 Beats per minute	Standard Deviation 7.42
Part 2: GSK2879552	Part 1: Change From Baseline in Heart Rate at Indicated Time-points	Cycle 2, Day 1, n=3	-6.3 Beats per minute	Standard Deviation 2.89
Part 2: GSK2879552	Part 1: Change From Baseline in Heart Rate at Indicated Time-points	Cycle 3, Day 1, n=3	-1.0 Beats per minute	Standard Deviation 9
Part 2: GSK2879552	Part 1: Change From Baseline in Heart Rate at Indicated Time-points	Cycle 4, Day 1, n=2	-2.0 Beats per minute	Standard Deviation 8.49
Part 2: GSK2879552	Part 1: Change From Baseline in Heart Rate at Indicated Time-points	Cycle 5, Day 1, n=1	-1.0 Beats per minute	—

Primary

Part 1: Change From Baseline in Hematocrit at Indicated Time-points

Blood samples were collected from participants for evaluation of hematology parameters including Hematocrit. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

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 (MEAN)	Dispersion
Part 2: GSK2879552	Part 1: Change From Baseline in Hematocrit at Indicated Time-points	Cycle 2, Day 1, n=3	-0.014 Proportion of red blood cells in blood	Standard Deviation 0.0396
Part 2: GSK2879552	Part 1: Change From Baseline in Hematocrit at Indicated Time-points	Cycle 2, Day 7, n=3	0.007 Proportion of red blood cells in blood	Standard Deviation 0.0448
Part 2: GSK2879552	Part 1: Change From Baseline in Hematocrit at Indicated Time-points	Cycle 2, Day 15, n=3	0.002 Proportion of red blood cells in blood	Standard Deviation 0.052
Part 2: GSK2879552	Part 1: Change From Baseline in Hematocrit at Indicated Time-points	Cycle 1, Day 1, n=5	0.001 Proportion of red blood cells in blood	Standard Deviation 0.0334
Part 2: GSK2879552	Part 1: Change From Baseline in Hematocrit at Indicated Time-points	Cycle 1, Day 7, n=5	-0.008 Proportion of red blood cells in blood	Standard Deviation 0.0525
Part 2: GSK2879552	Part 1: Change From Baseline in Hematocrit at Indicated Time-points	Cycle 1, Day 15, n=4	-0.018 Proportion of red blood cells in blood	Standard Deviation 0.0401
Part 2: GSK2879552	Part 1: Change From Baseline in Hematocrit at Indicated Time-points	Cycle 1, Day 22, n=3	0.007 Proportion of red blood cells in blood	Standard Deviation 0.01
Part 2: GSK2879552	Part 1: Change From Baseline in Hematocrit at Indicated Time-points	Cycle 2, Day 22, n=3	-0.009 Proportion of red blood cells in blood	Standard Deviation 0.0206
Part 2: GSK2879552	Part 1: Change From Baseline in Hematocrit at Indicated Time-points	Cycle 3, Day 1, n=3	-0.008 Proportion of red blood cells in blood	Standard Deviation 0.0244
Part 2: GSK2879552	Part 1: Change From Baseline in Hematocrit at Indicated Time-points	Cycle 4, Day 1, n=2	0.024 Proportion of red blood cells in blood	Standard Deviation 0.0191
Part 2: GSK2879552	Part 1: Change From Baseline in Hematocrit at Indicated Time-points	Cycle 5, Day 1, n=1	0.023 Proportion of red blood cells in blood	—

Primary

Part 1: Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points

Blood samples were collected from participants for evaluation of hematology parameters including MCHC and Hb. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

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 (MEAN)	Dispersion
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points	MCHC, Cycle 1, Day 1, n=5	-10.400 Grams per liter	Standard Deviation 29.3053
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points	MCHC, Cycle 1, Day 7, n=4	-12.500 Grams per liter	Standard Deviation 35.819
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points	MCHC, Cycle 1, Day 15, n=3	0.333 Grams per liter	Standard Deviation 2.0817
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points	MCHC, Cycle 1, Day 22, n=3	0.000 Grams per liter	Standard Deviation 8.1854
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points	MCHC, Cycle 2, Day 1, n=3	3.667 Grams per liter	Standard Deviation 6.6583
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points	MCHC, Cycle 2, Day 7, n=3	-1.000 Grams per liter	Standard Deviation 12.49
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points	MCHC, Cycle 2, Day 15, n=3	0.000 Grams per liter	Standard Deviation 7.8102
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points	MCHC, Cycle 2, Day 22, n=3	-2.000 Grams per liter	Standard Deviation 8.6603
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points	MCHC, Cycle 3, Day 1, n=3	1.333 Grams per liter	Standard Deviation 6.0277
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points	MCHC, Cycle 4, Day 1, n=2	-3.500 Grams per liter	Standard Deviation 9.1924
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points	MCHC, Cycle 5, Day 1, n=1	-8.000 Grams per liter	—
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points	Hb, Cycle 1, Day 1, n=5	-2.000 Grams per liter	Standard Deviation 7
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points	Hb, Cycle 1, Day 7, n=5	-4.200 Grams per liter	Standard Deviation 11.3666
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points	Hb, Cycle 1, Day 15, n=4	-5.000 Grams per liter	Standard Deviation 11.804
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points	Hb, Cycle 1, Day 22, n=3	2.000 Grams per liter	Standard Deviation 2.6458
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points	Hb, Cycle 2, Day 1, n=3	-3.667 Grams per liter	Standard Deviation 12.5831
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points	Hb, Cycle 2, Day 7, n=3	2.000 Grams per liter	Standard Deviation 13.4536
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points	Hb, Cycle 2, Day 15, n=3	0.333 Grams per liter	Standard Deviation 16.563
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points	Hb, Cycle 2, Day 22, n=3	-3.000 Grams per liter	Standard Deviation 5.2915
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points	Hb, Cycle 3, Day 1, n=3	-2.333 Grams per liter	Standard Deviation 7.2342
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points	Hb, Cycle 4, Day 1, n=2	7.000 Grams per liter	Standard Deviation 4.2426
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points	Hb, Cycle 5, Day 1, n=1	6.000 Grams per liter	—

Primary

Part 1: Change From Baseline in Mean Corpuscular Hemoglobin (MCH) at Indicated Time-points

Blood samples were collected from participants for evaluation of hematology parameters including MCH. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

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 (MEAN)	Dispersion
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin (MCH) at Indicated Time-points	Cycle 1, Day 1, n=5	-1.100 Picogram	Standard Deviation 2.8679
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin (MCH) at Indicated Time-points	Cycle 1, Day 7, n=4	-1.350 Picogram	Standard Deviation 3.3
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin (MCH) at Indicated Time-points	Cycle 1, Day 15, n=3	-0.100 Picogram	Standard Deviation 1.1358
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin (MCH) at Indicated Time-points	Cycle 1, Day 22, n=3	0.067 Picogram	Standard Deviation 1.5308
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin (MCH) at Indicated Time-points	Cycle 2, Day 1, n=3	0.833 Picogram	Standard Deviation 1.5177
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin (MCH) at Indicated Time-points	Cycle 2, Day 7, n=3	1.067 Picogram	Standard Deviation 1.3796
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin (MCH) at Indicated Time-points	Cycle 2, Day 15, n=3	0.900 Picogram	Standard Deviation 1.9672
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin (MCH) at Indicated Time-points	Cycle 2, Day 22, n=3	0.767 Picogram	Standard Deviation 2.3798
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin (MCH) at Indicated Time-points	Cycle 3, Day 1, n=3	0.933 Picogram	Standard Deviation 3.0665
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin (MCH) at Indicated Time-points	Cycle 4, Day 1, n=2	1.950 Picogram	Standard Deviation 1.3435
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin (MCH) at Indicated Time-points	Cycle 5, Day 1, n=1	2.200 Picogram	—

Primary

Part 1: Change From Baseline in Mean Corpuscular Volume (MCV) at Indicated Time-points

Blood samples were collected from participants for evaluation of hematology parameters including MCV. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

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 (MEAN)	Dispersion
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Volume (MCV) at Indicated Time-points	Cycle 2, Day 7, n=3	3.500 Femtoliter	Standard Deviation 6.3592
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Volume (MCV) at Indicated Time-points	Cycle 1, Day 1, n=5	-0.280 Femtoliter	Standard Deviation 1.545
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Volume (MCV) at Indicated Time-points	Cycle 1, Day 7, n=4	-0.400 Femtoliter	Standard Deviation 1.9442
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Volume (MCV) at Indicated Time-points	Cycle 1, Day 15, n=3	-0.267 Femtoliter	Standard Deviation 3.6679
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Volume (MCV) at Indicated Time-points	Cycle 1, Day 22, n=3	0.400 Femtoliter	Standard Deviation 5.173
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Volume (MCV) at Indicated Time-points	Cycle 2, Day 1, n=3	1.667 Femtoliter	Standard Deviation 6.0003
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Volume (MCV) at Indicated Time-points	Cycle 2, Day 15, n=3	2.933 Femtoliter	Standard Deviation 7.3528
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Volume (MCV) at Indicated Time-points	Cycle 2, Day 22, n=3	2.900 Femtoliter	Standard Deviation 9
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Volume (MCV) at Indicated Time-points	Cycle 3, Day 1, n=3	2.700 Femtoliter	Standard Deviation 9.737
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Volume (MCV) at Indicated Time-points	Cycle 4, Day 1, n=2	6.750 Femtoliter	Standard Deviation 6.2933
Part 2: GSK2879552	Part 1: Change From Baseline in Mean Corpuscular Volume (MCV) at Indicated Time-points	Cycle 5, Day 1, n=1	8.500 Femtoliter	—

Primary

Part 1: Change From Baseline in Partial Pressure Carbon Dioxide (pCO2) at Indicated Time Points

Blood samples were collected from participants for evaluation of clinical chemistry parameters including pCO2. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and Day 1 of Cycle 1 (cycle of 28 days)

Population: All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed.

Arm	Measure	Value (MEAN)
Part 2: GSK2879552	Part 1: Change From Baseline in Partial Pressure Carbon Dioxide (pCO2) at Indicated Time Points	0.173 Kilopascal

Primary

Part 1: Change From Baseline in Percent Reticulocytes at Indicated Time-points

Blood samples were collected from participants for evaluation of hematology parameters including percent reticulocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1) (each cycle of 28 days)

Population: All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed.

Arm	Measure	Group	Value (MEAN)
Part 2: GSK2879552	Part 1: Change From Baseline in Percent Reticulocytes at Indicated Time-points	Cycle 1, Day 22	-0.100 Percentage of reticulocytes
Part 2: GSK2879552	Part 1: Change From Baseline in Percent Reticulocytes at Indicated Time-points	Cycle 2, Day 1	-0.100 Percentage of reticulocytes
Part 2: GSK2879552	Part 1: Change From Baseline in Percent Reticulocytes at Indicated Time-points	Cycle 1, Day 7	0.000 Percentage of reticulocytes
Part 2: GSK2879552	Part 1: Change From Baseline in Percent Reticulocytes at Indicated Time-points	Cycle 2, Day 7	0.000 Percentage of reticulocytes
Part 2: GSK2879552	Part 1: Change From Baseline in Percent Reticulocytes at Indicated Time-points	Cycle 2, Day 15	0.000 Percentage of reticulocytes
Part 2: GSK2879552	Part 1: Change From Baseline in Percent Reticulocytes at Indicated Time-points	Cycle 3, Day 1	-0.100 Percentage of reticulocytes
Part 2: GSK2879552	Part 1: Change From Baseline in Percent Reticulocytes at Indicated Time-points	Cycle 4, Day 1	-0.100 Percentage of reticulocytes

Primary

Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points

Blood samples were collected from participants for evaluation of hematology parameters including platelets, neutrophils, monocytes, lymphocytes, leucocyte, eosinophils and basophils. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

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 (MEAN)	Dispersion
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Leucocytes, Cycle 2, Day 1, n=3	0.433 10^9 cells per liter	Standard Deviation 0.7234
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Eosinophils, Cycle 1, Day 7, n=5	0.016 10^9 cells per liter	Standard Deviation 0.0252
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Basophils, Cycle 1, Day 1, n=5	0.004 10^9 cells per liter	Standard Deviation 0.008
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Basophils, Cycle 2, Day 22, n=3	0.000 10^9 cells per liter	Standard Deviation 0
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Platelets, Cycle 1, Day 1, n=5	-13.826 10^9 cells per liter	Standard Deviation 16.2868
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Platelets, Cycle 1, Day 7, n=5	-17.984 10^9 cells per liter	Standard Deviation 15.7398
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Platelets, Cycle 1, Day 15, n=4	-19.250 10^9 cells per liter	Standard Deviation 8.2614
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Platelets, Cycle 1, Day 22, n=3	-20.667 10^9 cells per liter	Standard Deviation 14.3643
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Platelets, Cycle 2, Day 1, n=3	-16.000 10^9 cells per liter	Standard Deviation 18.735
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Platelets, Cycle 2, Day 7, n=3	-21.333 10^9 cells per liter	Standard Deviation 28.3784
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Platelets, Cycle 2, Day 15, n=3	-24.333 10^9 cells per liter	Standard Deviation 15.3731
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Platelets, Cycle 2, Day 22, n=3	-24.667 10^9 cells per liter	Standard Deviation 19.3477
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Platelets, Cycle 3, Day 1, n=3	-17.000 10^9 cells per liter	Standard Deviation 14.1067
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Platelets, Cycle 4, Day 1, n=2	-13.000 10^9 cells per liter	Standard Deviation 4.2426
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Platelets, Cycle 5, Day 1, n=1	-11.000 10^9 cells per liter	—
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Neutrophils, Cycle 1, Day 1, n=5	-0.019 10^9 cells per liter	Standard Deviation 0.1298
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Neutrophils, Cycle 1, Day 7, n=5	0.035 10^9 cells per liter	Standard Deviation 0.2058
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Neutrophils, Cycle 1, Day 15, n=4	0.060 10^9 cells per liter	Standard Deviation 0.3282
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Neutrophils, Cycle 1, Day 22, n=3	0.100 10^9 cells per liter	Standard Deviation 0.1732
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Neutrophils, Cycle 2, Day 1, n=3	0.200 10^9 cells per liter	Standard Deviation 0.3
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Neutrophils, Cycle 2, Day 7, n=3	0.300 10^9 cells per liter	Standard Deviation 0.3606
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Neutrophils, Cycle 2, Day 15, n=3	0.333 10^9 cells per liter	Standard Deviation 0.3055
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Neutrophils, Cycle 2, Day 22, n=3	0.267 10^9 cells per liter	Standard Deviation 0.4041
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Neutrophils, Cycle 3, Day 1, n=3	0.267 10^9 cells per liter	Standard Deviation 0.3215
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Neutrophils, Cycle 4, Day 1, n=2	0.650 10^9 cells per liter	Standard Deviation 0.2121
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Neutrophils, Cycle 5, Day 1, n=1	0.800 10^9 cells per liter	—
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Monocytes, Cycle 1, Day 1, n=5	0.017 10^9 cells per liter	Standard Deviation 0.1359
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Monocytes, Cycle 1, Day 7, n=5	0.059 10^9 cells per liter	Standard Deviation 0.0853
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Monocytes, Cycle 1, Day 15, n=4	0.100 10^9 cells per liter	Standard Deviation 0.0816
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Monocytes, Cycle 1, Day 22, n=3	12.633 10^9 cells per liter	Standard Deviation 21.7086
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Monocytes, Cycle 2, Day 1, n=3	0.267 10^9 cells per liter	Standard Deviation 0.2517
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Monocytes, Cycle 2, Day 7, n=3	0.400 10^9 cells per liter	Standard Deviation 0.6083
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Monocytes, Cycle 2, Day 15, n=3	0.633 10^9 cells per liter	Standard Deviation 0.7095
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Monocytes, Cycle 2, Day 22, n=3	0.267 10^9 cells per liter	Standard Deviation 0.2517
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Monocytes, Cycle 3, Day 1, n=3	0.300 10^9 cells per liter	Standard Deviation 0.1732
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Monocytes, Cycle 4, Day 1, n=2	1.000 10^9 cells per liter	Standard Deviation 0.1414
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Monocytes, Cycle 5, Day 1, n=1	1.600 10^9 cells per liter	—
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Lymphocytes, Cycle 1, Day 1, n=5	-0.036 10^9 cells per liter	Standard Deviation 0.0924
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Lymphocytes, Cycle 1, Day 7, n=5	0.008 10^9 cells per liter	Standard Deviation 0.1761
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Lymphocytes, Cycle 1, Day 15, n=4	-0.073 10^9 cells per liter	Standard Deviation 0.0486
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Lymphocytes, Cycle 1, Day 22, n=3	-0.033 10^9 cells per liter	Standard Deviation 0.0577
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Lymphocytes, Cycle 2, Day 1, n=3	-0.067 10^9 cells per liter	Standard Deviation 0.1528
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Lymphocytes, Cycle 2, Day 7, n=3	-0.033 10^9 cells per liter	Standard Deviation 0.3055
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Lymphocytes, Cycle 2, Day 15, n=3	0.033 10^9 cells per liter	Standard Deviation 0.3786
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Lymphocytes, Cycle 2, Day 22, n=3	0.033 10^9 cells per liter	Standard Deviation 0.2082
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Lymphocytes, Cycle 3, Day 1, n=3	-0.067 10^9 cells per liter	Standard Deviation 0.3055
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Lymphocytes, Cycle 4, Day 1, n=2	0.200 10^9 cells per liter	Standard Deviation 0
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Lymphocytes, Cycle 5, Day 1, n=1	0.400 10^9 cells per liter	—
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Leucocytes, Cycle 1, Day 1, n=5	-0.054 10^9 cells per liter	Standard Deviation 0.172
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Leucocytes, Cycle 1, Day 7, n=5	0.154 10^9 cells per liter	Standard Deviation 0.3257
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Leucocytes, Cycle 1, Day 15, n=4	0.032 10^9 cells per liter	Standard Deviation 0.3208
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Leucocytes, Cycle 1, Day 22, n=3	0.267 10^9 cells per liter	Standard Deviation 0.5132
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Leucocytes, Cycle 2, Day 7, n=3	0.700 10^9 cells per liter	Standard Deviation 1.3748
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Leucocytes, Cycle 2, Day 15, n=3	1.033 10^9 cells per liter	Standard Deviation 1.4572
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Leucocytes, Cycle 2, Day 22, n=3	0.633 10^9 cells per liter	Standard Deviation 0.9292
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Leucocytes, Cycle 3, Day 1, n=3	0.633 10^9 cells per liter	Standard Deviation 0.9074
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Leucocytes, Cycle 4, Day 1, n=2	2.000 10^9 cells per liter	Standard Deviation 0
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Leucocytes, Cycle 5, Day 1, n=1	2.900 10^9 cells per liter	—
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Eosinophils, Cycle 1, Day 1, n=5	-0.000 10^9 cells per liter	Standard Deviation 0.0009
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Eosinophils, Cycle 1, Day 15, n=4	-0.008 10^9 cells per liter	Standard Deviation 0.015
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Eosinophils, Cycle 1, Day 22, n=3	0.000 10^9 cells per liter	Standard Deviation 0
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Eosinophils, Cycle 2, Day 1, n=3	0.000 10^9 cells per liter	Standard Deviation 0
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Eosinophils, Cycle 2, Day 7, n=3	0.000 10^9 cells per liter	Standard Deviation 0
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Eosinophils, Cycle 2, Day 15, n=3	0.000 10^9 cells per liter	Standard Deviation 0
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Eosinophils, Cycle 2, Day 22, n=3	0.000 10^9 cells per liter	Standard Deviation 0
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Eosinophils, Cycle 3, Day 1, n=3	0.000 10^9 cells per liter	Standard Deviation 0
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Eosinophils, Cycle 4, Day 1, n=2	0.050 10^9 cells per liter	Standard Deviation 0.0707
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Eosinophils, Cycle 5, Day 1, n=1	0.100 10^9 cells per liter	—
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Basophils, Cycle 1, Day 7, n=5	0.017 10^9 cells per liter	Standard Deviation 0.0323
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Basophils, Cycle 1, Day 15, n=4	0.003 10^9 cells per liter	Standard Deviation 0.005
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Basophils, Cycle 1, Day 22, n=3	0.000 10^9 cells per liter	Standard Deviation 0
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Basophils, Cycle 2, Day 1, n=3	0.000 10^9 cells per liter	Standard Deviation 0
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Basophils, Cycle 2, Day 7, n=3	0.000 10^9 cells per liter	Standard Deviation 0
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Basophils, Cycle 2, Day 15, n=3	0.000 10^9 cells per liter	Standard Deviation 0
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Basophils, Cycle 3, Day 1, n=3	0.000 10^9 cells per liter	Standard Deviation 0
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Basophils, Cycle 4, Day 1, n=2	0.050 10^9 cells per liter	Standard Deviation 0.0707
Part 2: GSK2879552	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points	Basophils, Cycle 5, Day 1, n=1	0.000 10^9 cells per liter	—

Primary

Part 1: Change From Baseline in Respiratory Rate at Indicated Time-points

Vital signs including respiratory rate was measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and Cycle 1 (Days 7, 15), Cycle 2 (Day 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

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 (MEAN)	Dispersion
Part 2: GSK2879552	Part 1: Change From Baseline in Respiratory Rate at Indicated Time-points	Cycle 1, Day 7, n=5	-0.4 Breaths per minute	Standard Deviation 1.14
Part 2: GSK2879552	Part 1: Change From Baseline in Respiratory Rate at Indicated Time-points	Cycle 1, Day 15, n=4	-0.5 Breaths per minute	Standard Deviation 1
Part 2: GSK2879552	Part 1: Change From Baseline in Respiratory Rate at Indicated Time-points	Cycle 2, Day 1, n=3	-1.0 Breaths per minute	Standard Deviation 1
Part 2: GSK2879552	Part 1: Change From Baseline in Respiratory Rate at Indicated Time-points	Cycle 3, Day 1, n=3	-0.3 Breaths per minute	Standard Deviation 1.53
Part 2: GSK2879552	Part 1: Change From Baseline in Respiratory Rate at Indicated Time-points	Cycle 4, Day 1, n=2	-0.5 Breaths per minute	Standard Deviation 0.71
Part 2: GSK2879552	Part 1: Change From Baseline in Respiratory Rate at Indicated Time-points	Cycle 5, Day 1, n=1	-1.0 Breaths per minute	—

Primary

Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time-points

Vital signs including SBP and DBP were measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and Cycle 1 (Days 7, 15), Cycle 2 (Day 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

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 (MEAN)	Dispersion
Part 2: GSK2879552	Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time-points	SBP, Cycle 1, Day 7, n=5	-10.2 Millimeters of mercury	Standard Deviation 4.76
Part 2: GSK2879552	Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time-points	SBP, Cycle 1, Day 15, n=4	-13.5 Millimeters of mercury	Standard Deviation 3.87
Part 2: GSK2879552	Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time-points	SBP, Cycle 2, Day 1, n=3	-4.7 Millimeters of mercury	Standard Deviation 3.79
Part 2: GSK2879552	Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time-points	SBP, Cycle 3, Day 1, n=3	-3.7 Millimeters of mercury	Standard Deviation 8.39
Part 2: GSK2879552	Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time-points	SBP, Cycle 4, Day 1, n=2	-5.0 Millimeters of mercury	Standard Deviation 2.83
Part 2: GSK2879552	Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time-points	SBP, Cycle 5, Day 1, n=1	-6.0 Millimeters of mercury	—
Part 2: GSK2879552	Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time-points	DBP, Cycle 1, Day 7, n=5	-2.6 Millimeters of mercury	Standard Deviation 8.62
Part 2: GSK2879552	Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time-points	DBP, Cycle 1, Day 15, n=4	-3.5 Millimeters of mercury	Standard Deviation 4.04
Part 2: GSK2879552	Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time-points	DBP, Cycle 2, Day 1, n=3	-7.3 Millimeters of mercury	Standard Deviation 10.02
Part 2: GSK2879552	Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time-points	DBP, Cycle 3, Day 1, n=3	2.7 Millimeters of mercury	Standard Deviation 4.73
Part 2: GSK2879552	Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time-points	DBP, Cycle 4, Day 1, n=2	3.0 Millimeters of mercury	Standard Deviation 7.07
Part 2: GSK2879552	Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time-points	DBP, Cycle 5, Day 1, n=1	-4.0 Millimeters of mercury	—

Primary

Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points

Blood samples were collected from participants for evaluation of clinical chemistry parameters including Total Bilirubin, Direct Bilirubin, Creatinine and urate. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

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 (MEAN)	Dispersion
Part 2: GSK2879552	Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points	Creatinine Cycle 1, Day 15, n=4	17.238 Micromoles per liter (umol/L)	Standard Deviation 17.48
Part 2: GSK2879552	Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points	Urate Cycle 1, Day 7, n=2	5.948 Micromoles per liter (umol/L)	Standard Deviation 0
Part 2: GSK2879552	Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points	Urate Cycle 1, Day 22, n=1	35.688 Micromoles per liter (umol/L)	—
Part 2: GSK2879552	Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points	Urate Cycle 2, Day 1, n=1	65.428 Micromoles per liter (umol/L)	—
Part 2: GSK2879552	Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points	Total Bilirubin, Cycle 1, Day 1, n=4	-3.420 Micromoles per liter (umol/L)	Standard Deviation 5.4075
Part 2: GSK2879552	Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points	Total Bilirubin Cycle 1, Day 7, n=5	-1.094 Micromoles per liter (umol/L)	Standard Deviation 5.658
Part 2: GSK2879552	Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points	Total Bilirubin Cycle 1, Day 15, n=4	0.128 Micromoles per liter (umol/L)	Standard Deviation 6.6278
Part 2: GSK2879552	Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points	Total Bilirubin Cycle 1, Day 22, n=3	-1.710 Micromoles per liter (umol/L)	Standard Deviation 2.9618
Part 2: GSK2879552	Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points	Total Bilirubin Cycle 2, Day 1, n=3	-2.850 Micromoles per liter (umol/L)	Standard Deviation 3.5596
Part 2: GSK2879552	Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points	Total Bilirubin Cycle 3, Day 1, n=3	0.000 Micromoles per liter (umol/L)	Standard Deviation 3.42
Part 2: GSK2879552	Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points	Total Bilirubin Cycle 4, Day 1, n=2	-0.855 Micromoles per liter (umol/L)	Standard Deviation 3.6275
Part 2: GSK2879552	Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points	Total Bilirubin, Cycle 5, Day 1, n=1	-3.420 Micromoles per liter (umol/L)	—
Part 2: GSK2879552	Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points	Direct Bilirubin, Cycle 1, Day 1, n=1	1.368 Micromoles per liter (umol/L)	—
Part 2: GSK2879552	Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points	Creatinine, Cycle 1, Day 1, n=4	16.133 Micromoles per liter (umol/L)	Standard Deviation 25.5329
Part 2: GSK2879552	Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points	Creatinine Cycle 1, Day 7, n=5	4.066 Micromoles per liter (umol/L)	Standard Deviation 11.2271
Part 2: GSK2879552	Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points	Creatinine Cycle 1, Day 22, n=3	23.279 Micromoles per liter (umol/L)	Standard Deviation 18.55
Part 2: GSK2879552	Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points	Creatinine Cycle 2, Day 1, n=3	16.501 Micromoles per liter (umol/L)	Standard Deviation 16.6402
Part 2: GSK2879552	Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points	Creatinine Cycle 3, Day 1, n=3	15.912 Micromoles per liter (umol/L)	Standard Deviation 20.5613
Part 2: GSK2879552	Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points	Creatinine Cycle 4, Day 1, n=2	32.708 Micromoles per liter (umol/L)	Standard Deviation 8.7512
Part 2: GSK2879552	Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points	Creatinine, Cycle 5, Day 1, n=1	4.420 Micromoles per liter (umol/L)	—
Part 2: GSK2879552	Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points	Urate, Cycle 1, Day 1, n=1	41.636 Micromoles per liter (umol/L)	—
Part 2: GSK2879552	Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points	Urate Cycle 3, Day 1, n=1	89.220 Micromoles per liter (umol/L)	—
Part 2: GSK2879552	Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points	Urate Cycle 4, Day 1, n=1	59.480 Micromoles per liter (umol/L)	—

Primary

Part 1: Number of Participants With Abnormal Findings During Physical Examination

A complete physical examination included, at a minimum, assessment of the Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. A brief physical examination included, at a minimum assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). This analysis was planned but data was not captured in the database. Abnormal changes were captured as adverse events if they were clinically significant.

Time frame: Up to 2 years

Population: All Treated Subjects Population. This analysis was planned but data was not captured in the database.

Primary

Part 1: Number of Participants With Any Non-serious Adverse Event (Non-SAE), Serious AE (SAE), Dose Limiting Toxicities (DLT), Dose Reductions or Delays and Withdrawals Due to Toxicities

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. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or event associated with liver injury and impaired liver function were categorized as SAE. An event was considered a DLT if it occurred within the first 28 days of treatment, and met the DLT criteria unless it could be clearly established that the event was unrelated to treatment.

Time frame: Up to 2 years

Population: All Treated Subjects Population: All participants who received at least one dose of study treatment.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Part 2: GSK2879552	Part 1: Number of Participants With Any Non-serious Adverse Event (Non-SAE), Serious AE (SAE), Dose Limiting Toxicities (DLT), Dose Reductions or Delays and Withdrawals Due to Toxicities	Non-SAEs	5 Participants
Part 2: GSK2879552	Part 1: Number of Participants With Any Non-serious Adverse Event (Non-SAE), Serious AE (SAE), Dose Limiting Toxicities (DLT), Dose Reductions or Delays and Withdrawals Due to Toxicities	SAEs	1 Participants
Part 2: GSK2879552	Part 1: Number of Participants With Any Non-serious Adverse Event (Non-SAE), Serious AE (SAE), Dose Limiting Toxicities (DLT), Dose Reductions or Delays and Withdrawals Due to Toxicities	DLT	0 Participants
Part 2: GSK2879552	Part 1: Number of Participants With Any Non-serious Adverse Event (Non-SAE), Serious AE (SAE), Dose Limiting Toxicities (DLT), Dose Reductions or Delays and Withdrawals Due to Toxicities	Dose reductions or delays	0 Participants
Part 2: GSK2879552	Part 1: Number of Participants With Any Non-serious Adverse Event (Non-SAE), Serious AE (SAE), Dose Limiting Toxicities (DLT), Dose Reductions or Delays and Withdrawals Due to Toxicities	Withdrawals due to toxicities	0 Participants

Primary

Part 2: Percentage of Participants With Investigator-assessed Best Response Assessed by Clinical Benefit Rate (CBR)

CBR was defined as the percentage of participants achieving a confirmed Complete Remission (CR) or Partial Remission (PR) or Marrow Complete Remission (mCR) or confirmed Hematologic Improvement (HI) or Stable Disease (SD) prior to new anti-cancer therapy and crossover on the All Treated Subjects Population. Participants with Not Evaluable or missing response were to be treated as non-responders. International Working Group (IWG) criteria, 2006 was to be used to evaluate response.

Time frame: Up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Primary

Part 2: Percentage of Participants With Investigator-assessed Best Response Assessed by Objective Response Rate (ORR)

Objective response rate was defined as the percentage of participants who achieved CR or PR or mCR or HI prior to new anti-cancer therapy on the All Treated Subjects Population. Participants with Not Evaluable or missing response were to be treated as non-responders. IWG criteria, 2006 was to be used to evaluate response.

Time frame: Up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 1: Duration of Response

Duration of response is defined as the subset of participants (responders) who show a response (CR, mCR, PR, or HI), the time from first documented evidence of response until the first documented sign of disease progression or death. If no disease progression or death, the DOR was to be censored at last disease assessment.

Time frame: Up to 2 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as DOR could not be calculated because of the early termination of the study did not allow for this endpoint to be observed.

Secondary

Part 1: Number of Participants With Documented Platelet and Red Blood Cell (RBC) Transfusions Per Month

Number of participants with documented platelet and RBC transfusions have been presented.

Time frame: Up to 2 years

Population: All Treated Subjects Population

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Part 2: GSK2879552	Part 1: Number of Participants With Documented Platelet and Red Blood Cell (RBC) Transfusions Per Month	Platelets transfusion	5 Participants
Part 2: GSK2879552	Part 1: Number of Participants With Documented Platelet and Red Blood Cell (RBC) Transfusions Per Month	RBC transfusion	4 Participants
Part 2: GSK2879552	Part 1: Number of Participants With Documented Platelet and Red Blood Cell (RBC) Transfusions Per Month	RBC concentrated transfusion	1 Participants

Secondary

Part 1: Overall Survival

Overall survival (OS) is defined as the time from first treatment dose until death due to any reason. For the analysis of overall survival (OS), the last date of known contact was used for those participants who had not died at the time of analysis; such participants were considered censored.

Time frame: Up to 2 years

Population: All Treated Subjects Population

Arm	Measure	Value (MEDIAN)
Part 2: GSK2879552	Part 1: Overall Survival	22.4 Weeks

Secondary

Part 1: Percentage of Participants With Investigator-assessed Best Response Assessed by Clinical Benefit Rate (CBR)

Clinical Benefit Rate was defined as the percentage of participants achieving a confirmed Complete Remission (CR) or Partial Remission (PR) or Marrow Complete Remission (mCR) or confirmed Hematologic Improvement (HI) or Stable Disease (SD) prior to new anti-cancer therapy and crossover on the All Treated Subjects Population. Participants with Not Evaluable or missing response were treated as non-responders. International Working Group (IWG) criteria, 2006 was used to evaluate response.

Time frame: Up to 2 years

Population: All Treated Subjects Population

Arm	Measure	Value (NUMBER)
Part 2: GSK2879552	Part 1: Percentage of Participants With Investigator-assessed Best Response Assessed by Clinical Benefit Rate (CBR)	40 Percentage of Participants

Secondary

Part 1: Percentage of Participants With Investigator-assessed Best Response Assessed by Objective Response Rate (ORR)

Objective Response Rate was defined as the percentage of participants who achieved Complete Remission (CR) or Partial Remission (PR) or Marrow Complete Remission (mCR) or confirmed Hematologic Improvement (HI) prior to new anti-cancer therapy on the All Treated Subjects Population. Participants with Not Evaluable or missing response were treated as non-responders. International Working Group (IWG) criteria, 2006 was used to evaluate response.

Time frame: Up to 2 years

Population: All Treated Subjects Population

Arm	Measure	Value (NUMBER)
Part 2: GSK2879552	Part 1: Percentage of Participants With Investigator-assessed Best Response Assessed by Objective Response Rate (ORR)	20 Percentage of Participants

Secondary

Part 1: Plasma Concentration of Azacitidine

Blood samples were to be collected at indicated time points to evaluate concentration of Azacitidine.

Time frame: Cycle 1, Day 1: pre-dose, 0.5, 1, 3 hour; pre-dose on Days 2,4; Day 7: pre-dose, 0.5, 1, 3 hour; Day 15: pre-dose, 0.5-1 hour post-dose; pre-dose on Day 22; Cycle 2: pre-dose on Days 1, 7, 15, 22; Pre-dose on Day 1 of Cycles 3,4,5 (each cycle of 28 days)

Population: PK Concentration Population. Data was not collected due to blood samples were not collected as participants were not enrolled in GSK2879552 + Azacitidine arm due to early termination of the study.

Secondary

Part 1: Plasma Concentration of GSK2879552

Blood samples were collected at indicated time points to evaluate concentration of GSK2879552. Each Pharmacokinetic (PK) sample was collected as close as possible to the planned time relative to the dose (i.e., time zero) administered to the participant on PK days. PK Concentration Population consisted of all participants in the All Treated Subject Population for whom a blood sample for pharmacokinetics was obtained and analyzed.

Population: PK Concentration 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 (MEAN)	Dispersion
Part 2: GSK2879552	Part 1: Plasma Concentration of GSK2879552	Cycle 1, Day 1, 3 hour, n=5	6.40 Nanograms per milliliter	Standard Deviation 1.99
Part 2: GSK2879552	Part 1: Plasma Concentration of GSK2879552	Cycle 1, Day 2, pre-dose, n=5	1.03 Nanograms per milliliter	Standard Deviation 0.409
Part 2: GSK2879552	Part 1: Plasma Concentration of GSK2879552	Cycle 2, Day 1, pre-dose, n=3	2.16 Nanograms per milliliter	Standard Deviation 0.843
Part 2: GSK2879552	Part 1: Plasma Concentration of GSK2879552	Cycle 2, Day 7, pre-dose, n=3	1.81 Nanograms per milliliter	Standard Deviation 0.585
Part 2: GSK2879552	Part 1: Plasma Concentration of GSK2879552	Cycle 4, Day 1, pre-dose, n=2	1.63 Nanograms per milliliter	Standard Deviation 0.085
Part 2: GSK2879552	Part 1: Plasma Concentration of GSK2879552	Cycle 1, Day 1, pre-dose, n=5	0.00 Nanograms per milliliter	—
Part 2: GSK2879552	Part 1: Plasma Concentration of GSK2879552	Cycle 1, Day 1, 0.5 hour, n=4	11.79 Nanograms per milliliter	Standard Deviation 9.27
Part 2: GSK2879552	Part 1: Plasma Concentration of GSK2879552	Cycle 1, Day 1, 1 hour, n=5	8.18 Nanograms per milliliter	Standard Deviation 4.83
Part 2: GSK2879552	Part 1: Plasma Concentration of GSK2879552	Cycle 1, Day 4, pre-dose, n=5	1.87 Nanograms per milliliter	Standard Deviation 0.716
Part 2: GSK2879552	Part 1: Plasma Concentration of GSK2879552	Cycle 1, Day 7, pre-dose, n=5	1.97 Nanograms per milliliter	Standard Deviation 0.553
Part 2: GSK2879552	Part 1: Plasma Concentration of GSK2879552	Cycle 1, Day 7, 0.5 hour, n=5	9.58 Nanograms per milliliter	Standard Deviation 8.395
Part 2: GSK2879552	Part 1: Plasma Concentration of GSK2879552	Cycle 1, Day 7, 1 hour, n=5	9.17 Nanograms per milliliter	Standard Deviation 4.4777
Part 2: GSK2879552	Part 1: Plasma Concentration of GSK2879552	Cycle 1, Day 7, 3 hour, n=5	8.58 Nanograms per milliliter	Standard Deviation 3.595
Part 2: GSK2879552	Part 1: Plasma Concentration of GSK2879552	Cycle 1, Day 15, pre-dose, n=3	2.00 Nanograms per milliliter	Standard Deviation 0.798
Part 2: GSK2879552	Part 1: Plasma Concentration of GSK2879552	Cycle 1, Day 15, 0.5-1 hour, n=3	13.39 Nanograms per milliliter	Standard Deviation 0.798
Part 2: GSK2879552	Part 1: Plasma Concentration of GSK2879552	Cycle 1, Day 22, pre-dose, n=3	1.89 Nanograms per milliliter	Standard Deviation 0.723
Part 2: GSK2879552	Part 1: Plasma Concentration of GSK2879552	Cycle 2, Day 15, pre-dose, n=3	2.33 Nanograms per milliliter	Standard Deviation 1.135
Part 2: GSK2879552	Part 1: Plasma Concentration of GSK2879552	Cycle 2, Day 22, pre-dose, n=3	2.11 Nanograms per milliliter	Standard Deviation 0.709
Part 2: GSK2879552	Part 1: Plasma Concentration of GSK2879552	Cycle 3, Day 1, pre-dose, n=3	1.99 Nanograms per milliliter	Standard Deviation 0.802
Part 2: GSK2879552	Part 1: Plasma Concentration of GSK2879552	Cycle 5, Day 1, pre-dose, n=1	1.97 Nanograms per milliliter	—

Secondary

Part 1: Progression-free Survival

Progression-free survival (PFS) is defined as the time from first treatment dose until the first documented sign of disease progression or death. If the participant missed more than one visit prior to the date of documented events, PFS was censored at the last adequate assessment prior to missing. Otherwise, if the participant did not have a documented date of events, PFS was censored at the date of the last adequate assessment.

Time frame: Up to 2 years

Population: All Treated Subjects Population

Arm	Measure	Value (MEDIAN)
Part 2: GSK2879552	Part 1: Progression-free Survival	22.4 Weeks

Secondary

Part 1: Proportion of Participants With Disease Progression to Acute Myeloblastic Leukemia (AML)

The proportion of participants with disease progression to AML is defined as the percentage of participants experiencing AML on the All Treated Subjects Population.

Time frame: Up to 2 years

Population: All Treated Subjects Population

Arm	Measure	Value (NUMBER)
Part 2: GSK2879552	Part 1: Proportion of Participants With Disease Progression to Acute Myeloblastic Leukemia (AML)	40 Percentage of Participants

Secondary

Part 1: Time to AML Progression

Time to AML progression is defined as the time from first treatment dose until AML progression or crossover if using the All Treated Subjects Population. For the analysis of time to AML, if the participant did not experience AML, time to AML was censored at the last treatment prior to the initiation of anti-cancer therapy or crossover.

Time frame: Up to 2 years

Population: All Treated Subjects Population

Arm	Measure	Value (MEDIAN)
Part 2: GSK2879552	Part 1: Time to AML Progression	22.4 Weeks

Secondary

Part 2: Change From Baseline in Albumin and Protein at Indicated Time Points

Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including Albumin and Protein. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 2: Change From Baseline in ALT, ALP, AST, LDH and GGT at Indicated Time-points

Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including ALT, ALP, AST, LDH and GGT. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 2: Change From Baseline in Blast/Leukocytes at Indicated Time-points

Blood samples were to be collected from participants for evaluation of hematology parameters including blast/leukocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 2: Change From Baseline in Body Temperature at Indicated Time-points

Vital signs including body temperature was to be measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 2: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points

Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including Calcium, chloride, glucose, potassium, sodium, phosphate and urea nitrogen. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 2: Change From Baseline in ECG Mean Heart Rate at Indicated Time-points

Single 12-lead ECG was to be obtained at designated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 2: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time-points

Time frame: Baseline and up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 2: Change From Baseline in Erythrocytes at Indicated Time-points

Blood samples were to be collected from participants for evaluation of hematology parameters including erythrocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 2: Change From Baseline in Heart Rate at Indicated Time-points

Vital signs including heart rate was to be measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 2: Change From Baseline in Hematocrit at Indicated Time-points

Blood samples were to be collected from participants for evaluation of hematology parameters including Hematocrit. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 2: Change From Baseline in MCH at Indicated Time-points

Blood samples were to be collected from participants for evaluation of hematology parameters including MCH. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 2: Change From Baseline in MCHC and Hb at Indicated Time-points

Blood samples were to be collected from participants for evaluation of hematology parameters including MCHC and Hb. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 2: Change From Baseline in MCV at Indicated Time-points

Blood samples were to be collected from participants for evaluation of hematology parameters including MCV. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 2: Change From Baseline in pCO2 at Indicated Time Points

Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including pCO2. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 2: Change From Baseline in Percent Reticulocytes at Indicated Time-points

Blood samples were to be collected from participants for evaluation of hematology parameters including percent reticulocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 2: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points

Blood samples were to be collected from participants for evaluation of hematology parameters including platelets, neutrophils, monocytes, lymphocytes, leucocyte, eosinophils and basophils. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 2: Change From Baseline in Respiratory Rate at Indicated Time-points

Vital signs including respiratory rate was to be measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 2: Change From Baseline in SBP and DBP at Indicated Time-points

Vital signs including SBP and DBP were to be measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 2: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points

Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including Total Bilirubin, Direct Bilirubin, Creatinine and urate. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

Time frame: Baseline and up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 2: Duration of Response

Duration of response is defined as the time from first documented evidence of response until the first documented sign of disease progression or death. If no disease progression or death, the duration of response was to be censored at last disease assessment.

Time frame: Up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 2: Number of Participants With Abnormal Findings During Physical Examination

Time frame: Up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 2: Number of Participants With Any AEs and SAEs

Time frame: Up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 2: Number of Participants With Documented Platelet and Red Blood Cell (RBC) Transfusions Per Month

Number of participants with documented platelet and RBC transfusions were to be presented.

Time frame: Up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 2: Overall Survival

Overall survival is defined as the time from first treatment dose until death due to any reason. For the analysis of overall survival, the last date of known contact was to be used for those participants who had not died at the time of analysis; such participants were to be considered censored.

Time frame: Up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 2: Percentage of Participants With Disease Progression to AML

The percentage of participants experiencing AML on the All Treated Subjects Population was to be presented.

Time frame: Up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 2: Plasma Clearance (CL/F) of GSK2879552

Blood samples were to be collected at indicated time points to evaluate CL/F of GSK2879552. Each PK sample was to be collected as close as possible to the planned time relative to the dose (i.e., time zero) administered to the participant on PK days.

Time frame: Cycle 1, Day 1: pre-dose, 0.5, 1, 3 hour; pre-dose on Day 4; Day 7: pre-dose, 0.5, 1, 3 hour; Day 15: pre-dose, 0.5-1 hour post-dose; pre-dose on Day 22; Cycle 2: pre-dose on Days 1, 7, 15, 22; Pre-dose on Day 1 of Cycles 3 to 1 (each cycle of 28 days)

Population: PK Concentration Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 2: Progression-free Survival

Progression-free survival is defined as the time from first treatment dose until the first documented sign of disease progression or death. If the participant missed more than one visit prior to the date of documented events, PFS was to be censored at the last adequate assessment prior to missing. Otherwise, if the participant did not have a documented date of events, PFS was to be censored at the date of the last adequate assessment.

Time frame: Up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Secondary

Part 2: Time to AML Progression

Time to AML progression is defined as the time from first treatment dose until AML progression or crossover if using the All Treated Subjects Population. For the analysis of time to AML, if the participant did not experience AML, time to AML was to be censored at the last treatment prior to the initiation of anti-cancer therapy or crossover.

Time frame: Up to 2.5 years

Population: All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

Safety, Clinical Activity, Pharmacokinetics (PK) and Pharmacodynamics Study of GSK2879552, Alone or With Azacitidine, in Subjects With High Risk Myelodysplastic Syndromes (MDS)

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points

Part 1: Change From Baseline in Albumin and Protein at Indicated Time Points

Part 1: Change From Baseline in Blast/Leukocytes at Indicated Time-points

Part 1: Change From Baseline in Body Temperature at Indicated Time-points

Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points

Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points

Part 1: Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate at Indicated Time-points

Part 1: Change From Baseline in Erythrocytes at Indicated Time-points

Part 1: Change From Baseline in Heart Rate at Indicated Time-points

Part 1: Change From Baseline in Hematocrit at Indicated Time-points

Part 1: Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points

Part 1: Change From Baseline in Mean Corpuscular Hemoglobin (MCH) at Indicated Time-points

Part 1: Change From Baseline in Mean Corpuscular Volume (MCV) at Indicated Time-points

Part 1: Change From Baseline in Partial Pressure Carbon Dioxide (pCO2) at Indicated Time Points

Part 1: Change From Baseline in Percent Reticulocytes at Indicated Time-points

Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points

Part 1: Change From Baseline in Respiratory Rate at Indicated Time-points

Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time-points

Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points

Part 1: Number of Participants With Abnormal Findings During Physical Examination

Part 1: Number of Participants With Any Non-serious Adverse Event (Non-SAE), Serious AE (SAE), Dose Limiting Toxicities (DLT), Dose Reductions or Delays and Withdrawals Due to Toxicities

Part 2: Percentage of Participants With Investigator-assessed Best Response Assessed by Clinical Benefit Rate (CBR)

Part 2: Percentage of Participants With Investigator-assessed Best Response Assessed by Objective Response Rate (ORR)

Part 1: Duration of Response

Part 1: Number of Participants With Documented Platelet and Red Blood Cell (RBC) Transfusions Per Month

Part 1: Overall Survival

Part 1: Percentage of Participants With Investigator-assessed Best Response Assessed by Clinical Benefit Rate (CBR)

Part 1: Percentage of Participants With Investigator-assessed Best Response Assessed by Objective Response Rate (ORR)

Part 1: Plasma Concentration of Azacitidine

Part 1: Plasma Concentration of GSK2879552

Part 1: Progression-free Survival

Part 1: Proportion of Participants With Disease Progression to Acute Myeloblastic Leukemia (AML)

Part 1: Time to AML Progression

Part 2: Change From Baseline in Albumin and Protein at Indicated Time Points

Part 2: Change From Baseline in ALT, ALP, AST, LDH and GGT at Indicated Time-points

Part 2: Change From Baseline in Blast/Leukocytes at Indicated Time-points

Part 2: Change From Baseline in Body Temperature at Indicated Time-points

Part 2: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points

Part 2: Change From Baseline in ECG Mean Heart Rate at Indicated Time-points

Part 2: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time-points

Part 2: Change From Baseline in Erythrocytes at Indicated Time-points

Part 2: Change From Baseline in Heart Rate at Indicated Time-points

Part 2: Change From Baseline in Hematocrit at Indicated Time-points

Part 2: Change From Baseline in MCH at Indicated Time-points

Part 2: Change From Baseline in MCHC and Hb at Indicated Time-points

Part 2: Change From Baseline in MCV at Indicated Time-points

Part 2: Change From Baseline in pCO2 at Indicated Time Points

Part 2: Change From Baseline in Percent Reticulocytes at Indicated Time-points

Part 2: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points

Part 2: Change From Baseline in Respiratory Rate at Indicated Time-points

Part 2: Change From Baseline in SBP and DBP at Indicated Time-points

Part 2: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points

Part 2: Duration of Response

Part 2: Number of Participants With Abnormal Findings During Physical Examination

Part 2: Number of Participants With Any AEs and SAEs

Part 2: Number of Participants With Documented Platelet and Red Blood Cell (RBC) Transfusions Per Month

Part 2: Overall Survival