Investigation of GSK2879552 in Subjects With Relapsed/Refractory Small Cell Lung Carcinoma

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02034123
• Collaborator: (none)
• Enrollment: 29
• Locations: 8
• Arms: 2
• Actual Duration (Months): 38.4
• Patients Per Site: 3.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

GSK2879552 is a potent, selective, mechanism-based inactivator of Lysine Specific Demethylase 1 (LSD1)/ CoRepressor for Element-1-Silencing Transcription factor (CoREST) activity. This is a phase I, open-label, multi-center, non-randomized, 2-part first time in human (FTIH) study for GSK2879552. Part 1 is a dose escalation phase to determine the recommended phase 2 dose (RP2D) for GSK2879552 based on the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) profiles observed after oral administration of GSK2879552. Any dose level(s) may be expanded up to 12 subjects in order to collect additional data on PK and PD.The safety and PK/PD data will be reviewed prior to the dose decision, and the dose escalation will be guided by the Neuenschwander -continuous reassessment method (N-CRM). Built-in safety constraints are in place to prevent exposing subjects to undue risk of toxicity. Once RP2D is identified, an expansion cohort (Part 2) of up to 30 subjects will be enrolled to further evaluate the clinical activity and tolerability of GSK2879552 in subjects with relapsed/refractory SCLC.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Small Cell	Drug: GSK2879552	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Open-label, Dose Escalation Study to Investigate The Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK2879552 Given Orally in Subjects With Relapsed/Refractory Small Cell Lung Carcinoma
• Actual Study Start Date: Feb 4, 2014
• Actual Primary Completion Date: Apr 18, 2017
• Actual Study Completion Date: Apr 18, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Escalation Cohort The safety and PK/PD data will be reviewed prior to the dose decision, and the dose escalation will be guided by the Neuenschwander -continuous reassessment method (N-CRM).The dose escalation will complete when RP2D is determined. The RP2D will be the MTD or a lower dose that provides adequate PK exposure and biologic activity with superior tolerability.	Drug: GSK2879552; Subjects will receive GSK2879552orally with approximately 200 milliliter (mL) of water.
Experimental: Dose Expansion Cohort Once the RP2D has been determined, an expansion cohort of up to 30 subjects will be enrolled in order to better characterize the clinical activity and safety profile of the RP2D	Drug: GSK2879552; Subjects will receive GSK2879552orally with approximately 200 milliliter (mL) of water.

Outcome Measures

Primary Outcome Measures

1. Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs [Median of 7.286 weeks of drug exposure]

   An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth defect, other situations and is associated with liver injury or impaired liver function. The analysis was performed on All Treated Population which included all participants who received at least one dose of study treatment.

2. Part 1: Number of Participants With Dose Limiting Toxicities (DLT) [Median of 7.286 weeks of drug exposure]

   An event was considered a DLT if it occurs within the first 28 days of treatment, and meets one of the following criteria unless it can be clearly established that the event is unrelated to treatment: recurrent Grade 3 anemia after initial transfusion or Grade 3 anemia lasting > 7 days in participants who are not transfused, Grade 4 neutropenia, Grade 3 neutropenia > 7 days duration, febrile neutropenia as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, Grade 3 thrombocytopenia requiring dose reduction, Grade 4 thrombocytopenia lasting > 3 days or of any duration if associated with clinically significant bleeding, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 2 toxicity (at any time during treatment) and treatment delay of 14 days or greater due to unresolved drug-related toxicity.

3. Part 1: Number of Participants With Dose Reduction or Delays [Median of 7.286 weeks of drug exposure]

   The number of participants who had any dose reduction or delay have been presented. All dose reductions were due to AEs.

4. Part 1: Number of Participants Withdrawn Due to Toxicities [Median of 7.286 weeks of drug exposure]

   Participants were monitored from start of the study till the development of toxicity. The data for number of participants withdrawn due to toxicities has been presented.

5. Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline [Baseline and median of 7.286 weeks of drug exposure]

   Blood samples were collected for evaluation of clinical chemistry parameters including potassium, aspartate aminotransferase (AST), total bilirubin, creatinine, alanine aminotransferase (ALT), uric acid, glucose, gamma glutamyl transferase (GGT), albumin, sodium, calcium, alkaline phosphatase, and phosphorus, inorganic. Baseline value was defined as the most recent, non-missing value from a central laboratory prior to or on the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. The number of participants with any grade increase in clinical chemistry parameters have been presented. The clinical chemistry parameters for which any grade increase worst-case on-therapy value was reported have been only summarized. NA represents data was not available. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

6. Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline [Baseline and median of 7.286 weeks of drug exposure]

   Blood samples were collected for the analysis of hematology parameters including hemoglobin, lymphocytes, total neutrophils, platelet count and white blood cell (WBC) count. Baseline value was defined as the most recent, non-missing value from a central laboratory prior to or on the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. The number of participants with any grade increase in hematology parameters have been presented. The hematology parameters for which any grade increase worst-case on-therapy value was reported have been only summarized.

7. Part 1:Number of Participants With Critical Changes in Values of Vital Signs in Response to Drug [Median of 7.286 weeks of drug exposure]

   Vital sign measurements includes systolic blood pressure (SBP), diastolic blood pressure (DBP), temperature, respiration rate and heart rate. Vital signs were measured after resting for at least 5 minutes in a semi-supine position. The number of participants with critical changes in values of vital signs in response to drug have been presented.

8. Part 1: Number of Participants With Abnormal Findings for Electrocardiogram (ECG) Parameters [Median of 7.286 weeks of drug exposure]

   Single measurements of 12-lead ECGs were obtained in a semi-recumbent or supine position after at least a 5 minutes rest using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT (QTc) intervals. The number of participants with abnormal - not clinically significant and abnormal - clinically significant "worst-case on-therapy" value have been presented.

9. Part 1: Number of Participants With Abnormal Findings Undergoing Physical Examinations [Median of 7.286 weeks of drug exposure]

   The complete physical examination included assessments of the head, eyes, ears, nose, throat, skin, thyroid, neurological, lungs, cardiovascular, abdomen (liver and spleen), lymph nodes and extremities. A brief physical examination included assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). All abnormal physical examination findings were reported as AEs within the AE specific case report form (CRF) page. Hence, data was not captured separately for this outcome as number of participants with abnormal findings with respect to physical examinations. NA indicates data was not available as all abnormal physical examination findings were reported as AEs.

10. Part 2: Number of Participants Achieving Disease Control Rate at Week 16 [Week 16]

    Clinical response was planned to be assessed by the investigator using computer tomography or magnetic resonance imaging scans. Clinical response was defined as disease control rate based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 at Week 16. Disease control rate was defined as number of participants achieving complete response (CR), partial response (PR) and stable disease (SD) per RECIST version 1.1. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

Secondary Outcome Measures

1. Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) Following Single and Repeat Dose Administration of GSK2879552 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15]

   Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-t) following single (Day 1) and repeat dose (Day 15) administration of GSK2879552. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. The analysis was performed on Pharmacokinetic Population which included all participants in the All Treated Population for whom a pharmacokinetic sample was obtained and analyzed. NA represents data was not available. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

2. Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK2879552 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1]

   Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-infinity) following single (Day 1) dose administration of GSK2879552. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. NA represents data was not available.

3. Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK2879552 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Day 15]

   Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-tau) following repeat (Day 15) dose administration of GSK2879552. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. NA represents data was not available.

4. Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2879552 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15]

   Blood samples were collected from participants for pharmacokinetic analysis including Cmax following single (Day 1) and repeat dose (Day 15) administration of GSK2879552. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. NA represents data was not available. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

5. Part 1: Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of GSK2879552 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15]

   Blood samples were collected from participants for pharmacokinetic analysis including Tmax following single (Day 1) and repeat dose (Day 15) administration of GSK2879552. Tmax is the time to reach Cmax, determined directly from the concentration-time data. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. NA represents data was not available. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

6. Part 1: Apparent Terminal Phase Elimination Rate Constant (Lambda z) Following Single and Repeat Dose Administration of GSK2879552 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15]

   Blood samples were collected from participants for pharmacokinetic analysis including lambda z following single (Day 1) and repeat dose (Day 15) administration of GSK2879552. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. NA represents data was not available. The data for Day 15 was not computed due to the long half-life of GSK2879552 . Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

7. Part 1: Apparent Terminal Phase Half-life (T1/2) Following Single and Repeat Dose Administration of GSK2879552 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15]

   Blood samples were collected from participants for pharmacokinetic analysis including T1/2 following single (Day 1) and repeat dose (Day 15) administration of GSK2879552. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. NA represents data was not available. The data for Day 15 was not computed due to the long half-life of GSK2879552. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

8. Part 1: Accumulation Ratio Following Administration of GSK2879552 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15]

   The accumulation ratio was analyzed using analysis of variance (ANOVA) for AUC (0-tau) on Day 15 versus AUC (0-tau) on Day 1 by dose cohort. Only dose cohorts with repeat daily dosing were analyzed. The observed accumulation ratio (Ro) was determined based on AUC data to estimate the extent of accumulation after repeat dosing. The Ro of GSK2879552 was estimated by calculating the ratio of the geometric least squares (GLS) means of the pharmacokinetic parameter between Day 15 and Day 1 for all dose levels and the corresponding 90 percent confidence interval (CI) for each ratio.

9. Part 1: Time Invariance Ratio Following Administration of GSK2879552 [Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15]

   Time invariance was assessed to evaluate whether the pharmacokinetics remains unaltered after repeat dosing. The mixed effect model was fitted with day as a fixed effect and participant as a random effect for each treatment (dose) separately. AUC (0-tau) on Day 15 was compared to AUC (0-infinity) on Day 1 in order to assess time invariance for each dose. The ratio and 90 percent CI were calculated by back-transforming the difference between the LS means for the two days and associated 90 percent CI, for each dose. Only dose cohorts with repeat daily dosing were analyzed.

10. Part 1: Number of Participants Achieving Disease Control Rate at Week 16 [Week 16]

    The clinical activity of GSK2879552 given orally in participants with SCLC was evaluated by assessing disease control rate. Clinical response was assessed by the investigator using computer tomography or magnetic resonance imaging scans. Clinical response was defined as disease control rate (CR+PR+SD) based on RECIST version 1.1 at Week 16. Disease control rate was defined as number of participants achieving CR, PR and SD per RECIST version 1.1. The number of participants achieving disease control rate have been presented.

11. Part 1 :Median Effective Dose (ED50) of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and Dose [Baseline and median of 7.286 weeks of drug exposure]

    The pharmacokinetic/pharmacodynamic relationship of GSK2879552 administered orally was characterized by linear and/or non-linear mixed effect models. Only dose cohorts with repeat daily dosing were included in the analysis of platelet as a pharmacodynamic effect. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Percentage change from Baseline was defined as post-dose visit value minus Baseline value, divided by Baseline value and multiplied by 100. Estimates and standard error have been presented.

12. Part 1: ED50 of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and Cmax [Baseline and median of 7.286 weeks of drug exposure]

    The pharmacokinetic/pharmacodynamic relationship of GSK2879552 administered orally was characterized by linear and/or non-linear mixed effect models. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Percentage change from Baseline was defined as post-dose visit value minus Baseline value, divided by Baseline value and multiplied by 100. Only dose cohorts with repeat daily dosing were included in the analysis of platelet as a pharmacodynamic effect. Estimates and standard error have been presented.

13. Part 1: ED50 of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and AUC (0 to Infinity) [Baseline and median of 7.286 weeks of drug exposure]

    The pharmacokinetic/pharmacodynamic relationship of GSK2879552 administered orally was characterized by linear and/or non-linear mixed effect models. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Percentage change from Baseline was defined as post-dose visit value minus Baseline value, divided by Baseline value and multiplied by 100. Only dose cohorts with repeat daily dosing were included in the analysis of platelet as a pharmacodynamic effect. Estimates and standard error have been presented.

14. Part 2: Number of Participants With SAEs and Non-SAEs [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. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth defect, other situations and is associated with liver injury or impaired liver function. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

15. Part 2: Number of Participants With DLTs [Up to 2 years]

    An event was considered a DLT if it occured within the first 28 days of treatment, and meets one of the following criteria unless it can be clearly established that the event is unrelated to treatment: recurrent Grade 3 anemia after initial transfusion or Grade 3 anemia lasting > 7 days in participants who are not transfused, Grade 4 neutropenia, Grade 3 neutropenia > 7 days duration, febrile neutropenia as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, Grade 3 thrombocytopenia requiring dose reduction, Grade 4 thrombocytopenia lasting > 3 days or of any duration if associated with clinically significant bleeding, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 2 toxicity (at any time during treatment) and treatment delay of 14 days or greater due to unresolved drug-related toxicity. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

16. Part 2: Number of Participants With Dose Reduction or Delays [Up to 2 years]

    The number of participants who had any dose reduction or delay were planned to be analyzed. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

17. Part 2: Number of Participants Withdrawn Due to Toxicities [Up to 2 years]

    Participants were planned to be monitored from start of the study till the development of toxicity in Part 2. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

18. Part 2: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline [Baseline and up to 2 years]

    Blood samples were planned to be collected for evaluation of clinical chemistry parameters including potassium, aspartate aminotransferase (AST), total bilirubin, creatinine, ALT, uric acid, glucose, GGT, albumin, sodium, calcium, alkaline phosphatase, and phosphorus inorganic. Baseline value was defined as the most recent, non-missing value from a central laboratory prior to or on the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

19. Part 2: Number of Participants With Change in Hematology Toxicity Grade From Baseline [Baseline and up to 2 years]

    Blood samples were planned to be collected for the analysis of hematology parameters including hemoglobin, lymphocytes, total neutrophils, platelet count and white blood cell (WBC) count. Baseline value was defined as the most recent, non-missing value from a central laboratory prior to or on the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

20. Part 2:Number of Participants With Critical Changes in Values of Vital Signs in Response to Drug [Up to 2 years]

    Vital sign measurement includes SBP, DBP, temperature, respiration rate and heart rate. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

21. Part 2: Number of Participants With Abnormal Findings for ECG Parameters [Up to 2 years]

    Single measurements of 12-lead ECGs were planned to be obtained in a semi-recumbent or supine position after at least a 5 minutes rest using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

22. Part 2: Number of Participants With Abnormal Findings Undergoing Physical Examinations [Up to 2 years]

    The complete physical examination includes assessments of the head, eyes, ears, nose, throat, skin, thyroid, neurological, lungs, cardiovascular, abdomen (liver and spleen), lymph nodes and extremities. A brief physical examination includes assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

23. Part 2: Clearance Following Administration of GSK2879552 [Pre-dose, 0.5, and 3 hours post-dose on Day 1; Pre-dose on Day 8; Pre-dose, 0.5 to 1 hour, and 4 to 6 hours on Day 15; Pre-dose at Day 22 and up to every 4 weeks until Week 48]

    Blood samples were planned to be collected for population pharmacokinetic analysis of GSK2879552 including clearance. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

24. Part 2: Volume of Distribution Following Administration of GSK2879552 [Pre-dose, 0.5, and 3 hours post-dose on Day 1; Pre-dose on Day 8; Pre-dose, 0.5 to 1 hour, and 4 to 6 hours on Day 15; Pre-dose at Day 22 and up to every 4 weeks until Week 48]

    Blood samples were planned to be collected for population pharmacokinetic analysis of GSK2879552 including volume of distribution. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

25. Part 2: ED50 of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and Dose [Baseline and up to 2 years]

    The pharmacokinetic/pharmacodynamic relationship of GSK2879552 administered orally was planned to be characterized by linear and/or non-linear mixed effect models. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Percentage change from Baseline was defined as post-dose visit value minus Baseline value, divided by Baseline value and multiplied by 100. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

26. Part 2: ED50 of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and Cmax [Baseline and up to 2 years]

    The pharmacokinetic/pharmacodynamic relationship of GSK2879552 administered orally was planned to be characterized by linear and/or non-linear mixed effect models. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Percentage change from Baseline was defined as post-dose visit value minus Baseline value, divided by Baseline value and multiplied by 100. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

27. Part 2: ED50 of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and AUC (0 to Infinity) [Baseline and Up to 2 years]

    The pharmacokinetic/pharmacodynamic relationship of GSK2879552 administered orally was planned to be characterized by linear and/or non-linear mixed effect models. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Percentage change from Baseline was defined as post-dose visit value minus Baseline value, divided by Baseline value and multiplied by 100. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

28. Part 2: Duration of Response [Up to 2 years]

    Duration of response for participants is defined as the time from the first documented evidence of a PR or CR until the first documented sign of disease progression or death due to any cause. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

29. Part 2: Progression Free Survival (PFS) [Up to 2 years]

    PFS is defined as the interval between the first dose of study medication and the earliest date of disease progression or death due to any cause. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

30. Part 2: Percentage of Participants Achieving CR and PR [Up to 2 years]

    Overall response rate is defined as percentage of participants achieving CR and PR per RECIST version 1.1. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Provided signed written informed consent

• Males and females >=18 years of age (at the time consent is obtained).

• Histologically or cytologically confirmed diagnosis of small cell lung carcinoma. Subjects must have measurable disease per RECIST 1.1 (for Part 2 only).

• Recurrent or refractory disease after receiving at least one prior standard/approved platinum-containing chemotherapy regimen, or where standard therapy is refused. Part 2 only: Subjects must have recurrent disease after receiving a maximum of two prior chemotherapy regimens including at least one platinum containing regimen.

• Eastern Cooperative Oncology Group (ECOG) performance status of <= 1. (ECOG performance status of 0 or 1).

• Tumor tissue requirements: Availability of archival tissue, or willingness to undergo fresh biopsy at baseline; Enrollment in PK/PD cohort may be limited to subjects with disease amenable to pre- and post-dose biopsies, and willingness to undergo biopsy.

• All prior treatment-related toxicities must be National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.0 <=Grade 1 at the time of enrollment (except for alopecia)

• Adequate baseline organ function

• Women of childbearing potential must have a negative serum pregnancy test within 7 days of first dose of study treatment and agree to use effective contraception, as defined in protocol, 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 as described in protocol 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.

• Able to swallow and retain orally administered study treatment and does not have any clinically significant gastrointestinal (GI) abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach and/or bowels.

• French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

• Concurrent malignancy other than SCLC. History of other malignancy is allowed as long as there is no evidence of active disease or need for treatment.

• Currently receiving anti-cancer therapy. Exceptions: Zoledronic acid and denosumab to treat bone metastasis are allowed.

• Prior treatment with temozolomide, dacarbazine or procarbazine.

• Prior treatment with poly ADP ribose polymerase (PARP) inhibitors (e.g., olaparib, ABT-888).

• Baseline Montreal Cognitive Assessment (MOCA) score of 22 or lower.

• Received major surgery, radiotherapy, or immunotherapy within 4 weeks of GSK2879552 administration. Chemotherapy regimens with delayed toxicity within the last four weeks (six weeks for prior nitrosourea or mitomycin C). Chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity or palliative radiation to a limited area within the last two weeks.

• Administration of an investigational drug within 28 days or 5 half-lives, whichever is shorter preceding the first dose of study treatment(s) in this study.

• French subjects: The French subject has participated in any study using an investigational study treatment(s) during the previous 28 days.

• Subjects with current/a history of bleeding disorder or coagulopathy or who are at particularly high risk for bleeding complications.

• Requiring anticoagulants at therapeutic doses or platelet inhibitor.

• Current use of a prohibited medication or expected to require any of these medications during treatment with the investigational drug

• Evidence of severe or uncontrolled systemic diseases. Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the investigator

• Known active Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infections. Subjects with laboratory evidence of HBV clearance may be enrolled

• Leptomeningeal metastases or spinal cord compression due to disease.

• Subjects with previously untreated or uncontrolled brain metastases.

• Cardiac abnormalities

• Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GSK2879552 or LSD1 inhibitors that contraindicates their participation.

• Lactating female

• Consumption of Seville oranges, grapefruit, grapefruit hybrids, grapefruit juice, pommelos, or exotic citrus fruits, from 1 day prior to the first dose of study treatment(s) until the last dose of study drug.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Saint Louis	Missouri	United States	63110
2	GSK Investigational Site	Columbus	Ohio	United States	43210
3	GSK Investigational Site	Nashville	Tennessee	United States	37203
4	GSK Investigational Site	Villejuif cedex		France	94805
5	GSK Investigational Site	Barcelona		Spain	08035
6	GSK Investigational Site	Madrid		Spain	28034
7	GSK Investigational Site	Madrid		Spain	28040
8	GSK Investigational Site	Málaga		Spain	29010

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Study Protocol - Nov 22, 2016
• Statistical Analysis Plan - Jan 23, 2018

More Information

Publications

• Bauer TM, Besse B, Martinez-Marti A, Trigo JM, Moreno V, Garrido P, Ferron-Brady G, Wu Y, Park J, Collingwood T, Kruger RG, Mohammad HP, Ballas MS, Dhar A, Govindan R. Phase I, Open-Label, Dose-Escalation Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of GSK2879552 in Relapsed/Refractory SCLC. J Thorac Oncol. 2019 Oct;14(10):1828-1838. doi: 10.1016/j.jtho.2019.06.021. Epub 2019 Jun 28.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02034123
• Other Study ID Numbers: 200858; 2013-003451-38
• First Posted: Jan 13, 2014
• Last Update Posted: Dec 6, 2019
• Last Verified: Nov 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: First time in humans; Small cell lung carcinoma; Oncology; GSK2879552; LSD1 inhibitor
• Additional relevant MeSH terms: Carcinoma; Lung Neoplasms; Small Cell Lung Carcinoma; Carcinoma, Small Cell

Study Results

Participant Flow

Recruitment Details	This was planned as a 2-part, first time in human study in participants with relapsed/refractory small cell lung carcinoma. Part 1 was a dose escalation cohort and Part 2 was an expansion cohort. Participants were planned to receive GSK2879552 at a starting dose of 0.25 milligrams (mg) once daily for 28 days.
Pre-assignment Detail	This study was terminated early during Part 1 as the risk benefit in relapsed refractory SCLC did not favor continuation of the study. Data was collected only in Part 1 and no participants were enrolled in Part 2. A total of 29 participants enrolled and received treatment in Part 1. Of which 7 prematurely withdrawn and 22 completed study.

Arm/Group Title	Part 1:GSK2879552 0.25 mg Daily	Part 1:GSK2879552 0.5 mg Daily	Part 1:GSK2879552 1.0 mg Daily	Part 1:GSK2879552 1.5 mg Daily	Part 1: GSK2879552 2.0 mg Daily	Part 1: GSK2879552 3.0 mg Daily	Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 2:GSK2879552 0.25 mg Daily	Part 2:GSK2879552 0.5 mg Daily	Part 2:GSK2879552 1.0 mg Daily	Part 2:GSK2879552 1.5 mg Daily	Part 2: GSK2879552 2.0 mg Daily	Part 2: GSK2879552 3.0 mg Daily	Part 2: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 2: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 2: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants received GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants received GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants were planned to receive GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants were planned to receive GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Period Title: Part1(Median of 7.286 Weeks of Exposure)
STARTED	1	1	5	3	7	3	2	5	2	0	0	0	0	0	0	0	0	0
COMPLETED	1	1	5	1	5	3	2	4	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	0	0	0	2	2	0	0	1	2	0	0	0	0	0	0	0	0	0
Period Title: Part1(Median of 7.286 Weeks of Exposure)
STARTED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Part 1:GSK2879552 0.25 mg Daily	Part 1:GSK2879552 0.5 mg Daily	Part 1:GSK2879552 1.0 mg Daily	Part 1:GSK2879552 1.5 mg Daily	Part 1: GSK2879552 2.0 mg Daily	Part 1: GSK2879552 3.0 mg Daily	Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 2:GSK2879552 0.25 mg Daily	Part 2:GSK2879552 0.5 mg Daily	Part 2:GSK2879552 1.0 mg Daily	Part 2:GSK2879552 1.5 mg Daily	Part 2: GSK2879552 2.0 mg Daily	Part 2: GSK2879552 3.0 mg Daily	Part 2: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 2: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 2: GSK2879552 4.0 mg 4 Days on/10 Days Off	Total
Arm/Group Description	Participants received GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants received GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants were planned to receive GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants were planned to receive GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Total of all reporting groups
Overall Participants	1	1	5	3	7	3	2	5	2	0	0	0	0	0	0	0	0	0	29
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	78.0 (NA)	47.0 (NA)	63.8 (4.09)	56.7 (8.08)	62.4 (7.41)	60.3 (7.51)	53.5 (13.44)	58.8 (10.33)	61.5 (9.19)	60.6 (8.58)
Sex: Female, Male (Count of Participants)
Female	1 100%	1 100%	1 20%	0 0%	1 14.3%	2 66.7%	1 50%	3 60%	1 50%	11 Infinity
Male	0 0%	0 0%	4 80%	3 100%	6 85.7%	1 33.3%	1 50%	2 40%	1 50%	18 Infinity
Race/Ethnicity, Customized (Count of Participants)
African American/African Heritage	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 50%	0 0%	0 0%	1 Infinity
White-White/Caucasian/European Heritage	1 100%	1 100%	5 100%	3 100%	7 100%	3 100%	1 50%	5 100%	2 100%	28 Infinity

Outcome Measures

1. Primary Outcome

Title	Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs
Description	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth defect, other situations and is associated with liver injury or impaired liver function. The analysis was performed on All Treated Population which included all participants who received at least one dose of study treatment.
Time Frame	Median of 7.286 weeks of drug exposure

Outcome Measure Data

Analysis Population Description

All Treated Population

Arm/Group Title	Part 1:GSK2879552 0.25 mg Daily	Part 1:GSK2879552 0.5 mg Daily	Part 1:GSK2879552 1.0 mg Daily	Part 1:GSK2879552 1.5 mg Daily	Part 1: GSK2879552 2.0 mg Daily	Part 1: GSK2879552 3.0 mg Daily	Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants received GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants received GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	1	1	5	3	7	3	2	5	2
Any non-SAE	1 100%	1 100%	5 100%	2 66.7%	6 85.7%	3 100%	2 100%	5 100%	1 50%
Any SAE	0 0%	0 0%	0 0%	2 66.7%	2 28.6%	1 33.3%	0 0%	2 40%	2 100%

2. Primary Outcome

Title	Part 1: Number of Participants With Dose Limiting Toxicities (DLT)
Description	An event was considered a DLT if it occurs within the first 28 days of treatment, and meets one of the following criteria unless it can be clearly established that the event is unrelated to treatment: recurrent Grade 3 anemia after initial transfusion or Grade 3 anemia lasting > 7 days in participants who are not transfused, Grade 4 neutropenia, Grade 3 neutropenia > 7 days duration, febrile neutropenia as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, Grade 3 thrombocytopenia requiring dose reduction, Grade 4 thrombocytopenia lasting > 3 days or of any duration if associated with clinically significant bleeding, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 2 toxicity (at any time during treatment) and treatment delay of 14 days or greater due to unresolved drug-related toxicity.
Time Frame	Median of 7.286 weeks of drug exposure

Outcome Measure Data

Analysis Population Description

All Treated Population

Arm/Group Title	Part 1:GSK2879552 0.25 mg Daily	Part 1:GSK2879552 0.5 mg Daily	Part 1:GSK2879552 1.0 mg Daily	Part 1:GSK2879552 1.5 mg Daily	Part 1: GSK2879552 2.0 mg Daily	Part 1: GSK2879552 3.0 mg Daily	Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants received GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants received GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	1	1	5	3	7	3	2	5	2
Number [Participants]	0 0%	0 0%	0 0%	0 0%	1 14.3%	3 100%	0 0%	1 20%	0 0%

3. Primary Outcome

Title	Part 1: Number of Participants With Dose Reduction or Delays
Description	The number of participants who had any dose reduction or delay have been presented. All dose reductions were due to AEs.
Time Frame	Median of 7.286 weeks of drug exposure

Outcome Measure Data

Analysis Population Description

All Treated Population

Arm/Group Title	Part 1:GSK2879552 0.25 mg Daily	Part 1:GSK2879552 0.5 mg Daily	Part 1:GSK2879552 1.0 mg Daily	Part 1:GSK2879552 1.5 mg Daily	Part 1: GSK2879552 2.0 mg Daily	Part 1: GSK2879552 3.0 mg Daily	Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants received GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants received GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	1	1	5	3	7	3	2	5	2
Number [Participants]	1 100%	0 0%	0 0%	0 0%	3 42.9%	3 100%	1 50%	0 0%	0 0%

4. Primary Outcome

Title	Part 1: Number of Participants Withdrawn Due to Toxicities
Description	Participants were monitored from start of the study till the development of toxicity. The data for number of participants withdrawn due to toxicities has been presented.
Time Frame	Median of 7.286 weeks of drug exposure

Outcome Measure Data

Analysis Population Description

All Treated Population

Arm/Group Title	Part 1:GSK2879552 0.25 mg Daily	Part 1:GSK2879552 0.5 mg Daily	Part 1:GSK2879552 1.0 mg Daily	Part 1:GSK2879552 1.5 mg Daily	Part 1: GSK2879552 2.0 mg Daily	Part 1: GSK2879552 3.0 mg Daily	Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants received GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants received GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	1	1	5	3	7	3	2	5	2
Number [Participants]	0 0%	0 0%	0 0%	0 0%	1 14.3%	0 0%	0 0%	1 20%	1 50%

5. Primary Outcome

Title	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline
Description	Blood samples were collected for evaluation of clinical chemistry parameters including potassium, aspartate aminotransferase (AST), total bilirubin, creatinine, alanine aminotransferase (ALT), uric acid, glucose, gamma glutamyl transferase (GGT), albumin, sodium, calcium, alkaline phosphatase, and phosphorus, inorganic. Baseline value was defined as the most recent, non-missing value from a central laboratory prior to or on the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. The number of participants with any grade increase in clinical chemistry parameters have been presented. The clinical chemistry parameters for which any grade increase worst-case on-therapy value was reported have been only summarized. NA represents data was not available. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Baseline and median of 7.286 weeks of drug exposure

Outcome Measure Data

Analysis Population Description

All Treated Population

Arm/Group Title	Part 1:GSK2879552 0.25 mg Daily	Part 1:GSK2879552 0.5 mg Daily	Part 1:GSK2879552 1.0 mg Daily	Part 1:GSK2879552 1.5 mg Daily	Part 1: GSK2879552 2.0 mg Daily	Part 1: GSK2879552 3.0 mg Daily	Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants received GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants received GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	1	1	5	3	7	3	2	5	2
Albumin;n=1,1,5,3,5,3,2,5,2	1 100%	0 0%	4 80%	0 0%	0 0%	0 0%	0 0%	2 40%	1 50%
Alkaline Phosphatase;n=1,1,5,3,5,3,2,5,2	0 0%	0 0%	4 80%	0 0%	0 0%	1 33.3%	1 50%	2 40%	0 0%
ALT;n=1,1,5,3,5,3,2,5,2	1 100%	0 0%	2 40%	0 0%	1 14.3%	1 33.3%	1 50%	2 40%	1 50%
AST;n=1,1,5,3,5,3,2,5,2	1 100%	0 0%	3 60%	0 0%	0 0%	2 66.7%	1 50%	2 40%	1 50%
Total Bilirubin;n=1,1,5,3,5,3,2,5,2	0 0%	0 0%	1 20%	0 0%	0 0%	1 33.3%	0 0%	0 0%	0 0%
Calcium;n=1,1,5,3,5,3,2,5,2	0 0%	0 0%	2 40%	0 0%	0 0%	1 33.3%	1 50%	1 20%	0 0%
Calcium (hypercalcemia);n=1,1,5,3,5,3,2,5,2	0 0%	0 0%	2 40%	0 0%	0 0%	1 33.3%	0 0%	1 20%	0 0%
Calcium (hypocalcemia);n=1,1,5,3,5,3,2,5,2	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 50%	0 0%	0 0%
Creatinine;n=1,1,5,3,5,3,2,5,2	0 0%	0 0%	1 20%	1 33.3%	2 28.6%	1 33.3%	1 50%	0 0%	1 50%
GGT;n=1,1,5,3,5,3,2,5,2	1 100%	1 100%	4 80%	1 33.3%	2 28.6%	3 100%	1 50%	2 40%	1 50%
Glucose;n=1,1,5,3,6,3,2,5,2	1 100%	1 100%	2 40%	1 33.3%	4 57.1%	1 33.3%	1 50%	3 60%	1 50%
Glucose (hyperglycemia);n=1,1,5,3,6,3,2,5,2	1 100%	1 100%	2 40%	1 33.3%	4 57.1%	1 33.3%	1 50%	3 60%	1 50%
Glucose (hypoglycemia);n=1,1,5,3,6,3,2,5,2	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Potassium;n=1,1,5,2,5,3,2,5,2	1 100%	0 0%	2 40%	0 0%	1 14.3%	1 33.3%	0 0%	2 40%	0 0%
Potassium (hyperkalemia);n=1,1,5,2,5,3,2,5,2	0 0%	0 0%	1 20%	0 0%	1 14.3%	0 0%	0 0%	1 20%	0 0%
Potassium (hypokalemia);n=1,1,5,2,5,3,2,5,2	1 100%	0 0%	1 20%	0 0%	1 14.3%	1 33.3%	0 0%	2 40%	0 0%
Sodium;n=1,1,5,3,5,3,2,5,2	0 0%	0 0%	3 60%	0 0%	2 28.6%	1 33.3%	1 50%	1 20%	0 0%
Sodium (hypernatremia);n=1,1,5,3,5,3,2,5,2	0 0%	0 0%	0 0%	0 0%	1 14.3%	0 0%	0 0%	0 0%	0 0%
Sodium (hyponatremia);n=1,1,5,3,5,3,2,5,2	0 0%	0 0%	3 60%	0 0%	1 14.3%	1 33.3%	1 50%	1 20%	0 0%
Phosphorus, inorganic;n=1,1,5,3,5,3,2,5,2	0 0%	0 0%	3 60%	0 0%	2 28.6%	0 0%	0 0%	1 20%	0 0%
Uric acid;n=0,0,1,0,0,1,0,0,1	1 100%	1 100%	1 20%

6. Primary Outcome

Title	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline
Description	Blood samples were collected for the analysis of hematology parameters including hemoglobin, lymphocytes, total neutrophils, platelet count and white blood cell (WBC) count. Baseline value was defined as the most recent, non-missing value from a central laboratory prior to or on the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. The number of participants with any grade increase in hematology parameters have been presented. The hematology parameters for which any grade increase worst-case on-therapy value was reported have been only summarized.
Time Frame	Baseline and median of 7.286 weeks of drug exposure

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 1:GSK2879552 0.25 mg Daily	Part 1:GSK2879552 0.5 mg Daily	Part 1:GSK2879552 1.0 mg Daily	Part 1:GSK2879552 1.5 mg Daily	Part 1: GSK2879552 2.0 mg Daily	Part 1: GSK2879552 3.0 mg Daily	Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants received GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants received GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	1	1	5	3	6	3	2	5	2
Hemoglobin	1 100%	0 0%	3 60%	2 66.7%	4 57.1%	2 66.7%	0 0%	3 60%	1 50%
Hemoglobin (Increased)	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Hemoglobin (Anemia)	1 100%	0 0%	3 60%	2 66.7%	4 57.1%	2 66.7%	0 0%	3 60%	1 50%
Lymphocytes	0 0%	0 0%	3 60%	2 66.7%	2 28.6%	2 66.7%	1 50%	4 80%	1 50%
Lymphocytes (Increased)	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Lymphocytes (Decreased)	0 0%	0 0%	3 60%	2 66.7%	2 28.6%	2 66.7%	1 50%	4 80%	1 50%
Total Neutrophils	1 100%	0 0%	2 40%	0 0%	2 28.6%	2 66.7%	2 100%	1 20%	0 0%
Platelet count	1 100%	0 0%	3 60%	1 33.3%	5 71.4%	3 100%	1 50%	4 80%	0 0%
WBC count	1 100%	0 0%	2 40%	0 0%	2 28.6%	3 100%	2 100%	3 60%	0 0%

7. Primary Outcome

Title	Part 1:Number of Participants With Critical Changes in Values of Vital Signs in Response to Drug
Description	Vital sign measurements includes systolic blood pressure (SBP), diastolic blood pressure (DBP), temperature, respiration rate and heart rate. Vital signs were measured after resting for at least 5 minutes in a semi-supine position. The number of participants with critical changes in values of vital signs in response to drug have been presented.
Time Frame	Median of 7.286 weeks of drug exposure

Outcome Measure Data

Analysis Population Description

All Treated Population

Arm/Group Title	Part 1:GSK2879552 0.25 mg Daily	Part 1:GSK2879552 0.5 mg Daily	Part 1:GSK2879552 1.0 mg Daily	Part 1:GSK2879552 1.5 mg Daily	Part 1: GSK2879552 2.0 mg Daily	Part 1: GSK2879552 3.0 mg Daily	Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants received GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants received GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	1	1	5	3	7	3	2	5	2
Number [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

8. Primary Outcome

Title	Part 1: Number of Participants With Abnormal Findings for Electrocardiogram (ECG) Parameters
Description	Single measurements of 12-lead ECGs were obtained in a semi-recumbent or supine position after at least a 5 minutes rest using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT (QTc) intervals. The number of participants with abnormal - not clinically significant and abnormal - clinically significant "worst-case on-therapy" value have been presented.
Time Frame	Median of 7.286 weeks of drug exposure

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 1:GSK2879552 0.25 mg Daily	Part 1:GSK2879552 0.5 mg Daily	Part 1:GSK2879552 1.0 mg Daily	Part 1:GSK2879552 1.5 mg Daily	Part 1: GSK2879552 2.0 mg Daily	Part 1: GSK2879552 3.0 mg Daily	Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants received GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants received GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	1	1	5	3	5	3	2	5	1
Abnormal - not clinically significant	0 0%	1 100%	4 80%	1 33.3%	4 57.1%	1 33.3%	1 50%	5 100%	1 50%
Abnormal - clinically significant	0 0%	0 0%	0 0%	0 0%	2 28.6%	0 0%	0 0%	0 0%	0 0%

9. Primary Outcome

Title	Part 1: Number of Participants With Abnormal Findings Undergoing Physical Examinations
Description	The complete physical examination included assessments of the head, eyes, ears, nose, throat, skin, thyroid, neurological, lungs, cardiovascular, abdomen (liver and spleen), lymph nodes and extremities. A brief physical examination included assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). All abnormal physical examination findings were reported as AEs within the AE specific case report form (CRF) page. Hence, data was not captured separately for this outcome as number of participants with abnormal findings with respect to physical examinations. NA indicates data was not available as all abnormal physical examination findings were reported as AEs.
Time Frame	Median of 7.286 weeks of drug exposure

Outcome Measure Data

Analysis Population Description

All Treated Population

Arm/Group Title	Part 1:GSK2879552 0.25 mg Daily	Part 1:GSK2879552 0.5 mg Daily	Part 1:GSK2879552 1.0 mg Daily	Part 1:GSK2879552 1.5 mg Daily	Part 1: GSK2879552 2.0 mg Daily	Part 1: GSK2879552 3.0 mg Daily	Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants received GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants received GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	1	1	5	3	7	3	2	5	2
Number [Participants]	NA NaN	NA NaN	NA NaN	NA NaN	NA NaN	NA NaN	NA NaN	NA NaN	NA NaN

10. Primary Outcome

Title	Part 2: Number of Participants Achieving Disease Control Rate at Week 16
Description	Clinical response was planned to be assessed by the investigator using computer tomography or magnetic resonance imaging scans. Clinical response was defined as disease control rate based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 at Week 16. Disease control rate was defined as number of participants achieving complete response (CR), partial response (PR) and stable disease (SD) per RECIST version 1.1. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2:GSK2879552 0.25 mg Daily	Part 2:GSK2879552 0.5 mg Daily	Part 2:GSK2879552 1.0 mg Daily	Part 2:GSK2879552 1.5 mg Daily	Part 2: GSK2879552 2.0 mg Daily	Part 2: GSK2879552 3.0 mg Daily	Part 2: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 2: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 2: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants were planned to receive GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants were planned to receive GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	0	0	0	0	0	0	0	0	0

11. Secondary Outcome

Title	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) Following Single and Repeat Dose Administration of GSK2879552
Description	Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-t) following single (Day 1) and repeat dose (Day 15) administration of GSK2879552. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. The analysis was performed on Pharmacokinetic Population which included all participants in the All Treated Population for whom a pharmacokinetic sample was obtained and analyzed. NA represents data was not available. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population

Arm/Group Title	Part 1:GSK2879552 0.25 mg Daily	Part 1:GSK2879552 0.5 mg Daily	Part 1:GSK2879552 1.0 mg Daily	Part 1:GSK2879552 1.5 mg Daily	Part 1: GSK2879552 2.0 mg Daily	Part 1: GSK2879552 3.0 mg Daily	Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants received GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants received GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	1	1	5	3	7	3	2	5	2
Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	10.4 (NA)	21.6 (NA)	32.4 (15.7)	60.8 (13.8)	86.0 (57.6)	190.0 (29.6)	148.0 (29.9)	155.2 (29.0)	129.1 (26.2)
Day 15; n=1, 1, 5, 1, 5, 3,2, 5,0	27.0 (NA)	40.7 (NA)	53.6 (31.5)	91.1 (NA)	144.1 (64.6)	122.1 (30.4)	164.1 (7.8)	184.4 (40.4)

12. Secondary Outcome

Title	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK2879552
Description	Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-infinity) following single (Day 1) dose administration of GSK2879552. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. NA represents data was not available.
Time Frame	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 1:GSK2879552 0.25 mg Daily	Part 1:GSK2879552 0.5 mg Daily	Part 1:GSK2879552 1.0 mg Daily	Part 1:GSK2879552 1.5 mg Daily	Part 1: GSK2879552 2.0 mg Daily	Part 1: GSK2879552 3.0 mg Daily	Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants received GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants received GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	1	1	5	3	6	3	2	5	1
Geometric Mean (Geometric Coefficient of Variation) [Hour*Nanogram per milliliter]	14.5 (NA)	27.2 (NA)	40.0 (18.7)	70.7 (15.0)	108.6 (56.1)	206.3 (27.7)	163.6 (25.3)	182.9 (27.1)	180.9 (NA)

13. Secondary Outcome

Title	Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK2879552
Description	Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-tau) following repeat (Day 15) dose administration of GSK2879552. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. NA represents data was not available.
Time Frame	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Day 15

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 1:GSK2879552 0.25 mg Daily	Part 1:GSK2879552 0.5 mg Daily	Part 1:GSK2879552 1.0 mg Daily	Part 1:GSK2879552 1.5 mg Daily	Part 1: GSK2879552 2.0 mg Daily	Part 1: GSK2879552 3.0 mg Daily	Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants received GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants received GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	1	1	5	1	5	3	2	4	0
Geometric Mean (Geometric Coefficient of Variation) [Hour*Nanogram per milliliter]	27.3 (NA)	40.3 (NA)	53.3 (31.2)	91.1 (NA)	143.8 (64.2)	141.9 (32.4)	164.7 (8.2)	203.4 (37.2)

14. Secondary Outcome

Title	Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2879552
Description	Blood samples were collected from participants for pharmacokinetic analysis including Cmax following single (Day 1) and repeat dose (Day 15) administration of GSK2879552. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. NA represents data was not available. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population

Arm/Group Title	Part 1:GSK2879552 0.25 mg Daily	Part 1:GSK2879552 0.5 mg Daily	Part 1:GSK2879552 1.0 mg Daily	Part 1:GSK2879552 1.5 mg Daily	Part 1: GSK2879552 2.0 mg Daily	Part 1: GSK2879552 3.0 mg Daily	Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants received GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants received GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	1	1	5	3	7	3	2	5	2
Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	3.8 (NA)	2.9 (NA)	6.4 (17.3)	9.3 (12.2)	12.9 (36.6)	22.0 (42.9)	31.2 (26.8)	23.9 (20.8)	23.4 (68.8)
Day 15; n=1, 1, 5, 1, 5, 3, 2, 5, 0	3.4 (NA)	4.3 (NA)	6.9 (29.2)	13.8 (NA)	15.7 (39.4)	15.2 (23.1)	24.4 (21.5)	28.1 (7.7)

15. Secondary Outcome

Title	Part 1: Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of GSK2879552
Description	Blood samples were collected from participants for pharmacokinetic analysis including Tmax following single (Day 1) and repeat dose (Day 15) administration of GSK2879552. Tmax is the time to reach Cmax, determined directly from the concentration-time data. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. NA represents data was not available. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population

Arm/Group Title	Part 1:GSK2879552 0.25 mg Daily	Part 1:GSK2879552 0.5 mg Daily	Part 1:GSK2879552 1.0 mg Daily	Part 1:GSK2879552 1.5 mg Daily	Part 1: GSK2879552 2.0 mg Daily	Part 1: GSK2879552 3.0 mg Daily	Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants received GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants received GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	1	1	5	3	7	3	2	5	2
Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	0.5 (NA)	1.5 (NA)	0.5 (2.8)	1.3 (110.4)	0.8 (108.5)	1.6 (42.5)	0.8 (85.8)	1.2 (52.6)	0.7 (52.1)
Day 15; n=1, 1, 5, 1, 5, 3, 2, 5, 0	1.0 (NA)	1.5 (NA)	0.9 (65.1)	0.5 (NA)	1.1 (88.6)	1.5 (86.3)	1.4 (52.1)	1.0 (46.7)

16. Secondary Outcome

Title	Part 1: Apparent Terminal Phase Elimination Rate Constant (Lambda z) Following Single and Repeat Dose Administration of GSK2879552
Description	Blood samples were collected from participants for pharmacokinetic analysis including lambda z following single (Day 1) and repeat dose (Day 15) administration of GSK2879552. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. NA represents data was not available. The data for Day 15 was not computed due to the long half-life of GSK2879552 . Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population

Arm/Group Title	Part 1:GSK2879552 0.25 mg Daily	Part 1:GSK2879552 0.5 mg Daily	Part 1:GSK2879552 1.0 mg Daily	Part 1:GSK2879552 1.5 mg Daily	Part 1: GSK2879552 2.0 mg Daily	Part 1: GSK2879552 3.0 mg Daily	Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants received GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants received GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	1	1	5	3	7	3	2	5	2
Day 1; n= 1, 1, 5, 3, 6, 3, 2, 5, 1	0.0 (NA)	0.0 (NA)	0.0 (62.6)	0.1 (8.7)	0.0 (8.7)	0.0 (19.1)	0.1 (47.9)	0.1 (23.2)	0.1 (NA)

17. Secondary Outcome

Title	Part 1: Apparent Terminal Phase Half-life (T1/2) Following Single and Repeat Dose Administration of GSK2879552
Description	Blood samples were collected from participants for pharmacokinetic analysis including T1/2 following single (Day 1) and repeat dose (Day 15) administration of GSK2879552. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. NA represents data was not available. The data for Day 15 was not computed due to the long half-life of GSK2879552. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population

Arm/Group Title	Part 1:GSK2879552 0.25 mg Daily	Part 1:GSK2879552 0.5 mg Daily	Part 1:GSK2879552 1.0 mg Daily	Part 1:GSK2879552 1.5 mg Daily	Part 1: GSK2879552 2.0 mg Daily	Part 1: GSK2879552 3.0 mg Daily	Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants received GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants received GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	1	1	5	3	7	3	2	5	2
Day 1; n=1, 1, 5, 3, 6, 3, 2, 5, 1	16.9 (NA)	24.0 (NA)	17.3 (62.6)	8.8 (8.7)	18.1 (8.7)	15.4 (19.1)	11.5 (47.9)	8.9 (23.2)	8.4 (NA)

18. Secondary Outcome

Title	Part 1: Accumulation Ratio Following Administration of GSK2879552
Description	The accumulation ratio was analyzed using analysis of variance (ANOVA) for AUC (0-tau) on Day 15 versus AUC (0-tau) on Day 1 by dose cohort. Only dose cohorts with repeat daily dosing were analyzed. The observed accumulation ratio (Ro) was determined based on AUC data to estimate the extent of accumulation after repeat dosing. The Ro of GSK2879552 was estimated by calculating the ratio of the geometric least squares (GLS) means of the pharmacokinetic parameter between Day 15 and Day 1 for all dose levels and the corresponding 90 percent confidence interval (CI) for each ratio.
Time Frame	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 1:GSK2879552 1.0 mg Daily	Part 1: GSK2879552 2.0 mg Daily
Arm/Group Description	Participants received GSK2879552 with a dose of 1.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.
Measure Participants	5	4
Number (90% Confidence Interval) [Ratio of AUC]	1.917	1.652

19. Secondary Outcome

Title	Part 1: Time Invariance Ratio Following Administration of GSK2879552
Description	Time invariance was assessed to evaluate whether the pharmacokinetics remains unaltered after repeat dosing. The mixed effect model was fitted with day as a fixed effect and participant as a random effect for each treatment (dose) separately. AUC (0-tau) on Day 15 was compared to AUC (0-infinity) on Day 1 in order to assess time invariance for each dose. The ratio and 90 percent CI were calculated by back-transforming the difference between the LS means for the two days and associated 90 percent CI, for each dose. Only dose cohorts with repeat daily dosing were analyzed.
Time Frame	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 1:GSK2879552 1.0 mg Daily	Part 1: GSK2879552 2.0 mg Daily	Part 1: GSK2879552 3.0 mg Daily
Arm/Group Description	Participants received GSK2879552 with a dose of 1.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.
Measure Participants	5	5	3
Number (90% Confidence Interval) [Ratio of AUC]	1.332	1.206	0.688

20. Secondary Outcome

Title	Part 1: Number of Participants Achieving Disease Control Rate at Week 16
Description	The clinical activity of GSK2879552 given orally in participants with SCLC was evaluated by assessing disease control rate. Clinical response was assessed by the investigator using computer tomography or magnetic resonance imaging scans. Clinical response was defined as disease control rate (CR+PR+SD) based on RECIST version 1.1 at Week 16. Disease control rate was defined as number of participants achieving CR, PR and SD per RECIST version 1.1. The number of participants achieving disease control rate have been presented.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

All Treated Population.

Arm/Group Title	Part 1:GSK2879552 0.25 mg Daily	Part 1:GSK2879552 0.5 mg Daily	Part 1:GSK2879552 1.0 mg Daily	Part 1:GSK2879552 1.5 mg Daily	Part 1: GSK2879552 2.0 mg Daily	Part 1: GSK2879552 3.0 mg Daily	Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants received GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants received GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	1	1	5	3	7	3	2	5	2
Number [Participants]	1 100%	0 0%	0 0%	0 0%	1 14.3%	1 33.3%	1 50%	0 0%	0 0%

21. Secondary Outcome

Title	Part 1 :Median Effective Dose (ED50) of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and Dose
Description	The pharmacokinetic/pharmacodynamic relationship of GSK2879552 administered orally was characterized by linear and/or non-linear mixed effect models. Only dose cohorts with repeat daily dosing were included in the analysis of platelet as a pharmacodynamic effect. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Percentage change from Baseline was defined as post-dose visit value minus Baseline value, divided by Baseline value and multiplied by 100. Estimates and standard error have been presented.
Time Frame	Baseline and median of 7.286 weeks of drug exposure

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population

Arm/Group Title	Part 1: Participants With Repeat Daily Dosing
Arm/Group Description	Participants received repeat daily dosing with GSK2879552 with a starting dose of 0.25 mg once daily for 28 days. The doses were escalated to receive either 0.25 mg or 0.5 or 1 mg or 1.5 or 2 mg or 3 mg daily for 28 days.
Measure Participants	29
Mean (Standard Error) [Milligrams]	1.7444 (0.1436)

22. Secondary Outcome

Title	Part 1: ED50 of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and Cmax
Description	The pharmacokinetic/pharmacodynamic relationship of GSK2879552 administered orally was characterized by linear and/or non-linear mixed effect models. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Percentage change from Baseline was defined as post-dose visit value minus Baseline value, divided by Baseline value and multiplied by 100. Only dose cohorts with repeat daily dosing were included in the analysis of platelet as a pharmacodynamic effect. Estimates and standard error have been presented.
Time Frame	Baseline and median of 7.286 weeks of drug exposure

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population

Arm/Group Title	Part 1: Participants With Repeat Daily Dosing
Arm/Group Description	Participants received repeat daily dosing with GSK2879552 with a starting dose of 0.25 mg once daily for 28 days. The doses were escalated to receive either 0.25 mg or 0.5 or 1 mg or 1.5 or 2 mg or 3 mg daily for 28 days.
Measure Participants	29
Mean (Standard Error) [Nanogram per milliliter]	10.3948 (1.2666)

23. Secondary Outcome

Title	Part 1: ED50 of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and AUC (0 to Infinity)
Description	The pharmacokinetic/pharmacodynamic relationship of GSK2879552 administered orally was characterized by linear and/or non-linear mixed effect models. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Percentage change from Baseline was defined as post-dose visit value minus Baseline value, divided by Baseline value and multiplied by 100. Only dose cohorts with repeat daily dosing were included in the analysis of platelet as a pharmacodynamic effect. Estimates and standard error have been presented.
Time Frame	Baseline and median of 7.286 weeks of drug exposure

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population

Arm/Group Title	Part 1: Participants With Repeat Daily Dosing
Arm/Group Description	Participants received repeat daily dosing with GSK2879552 with a starting dose of 0.25 mg once daily for 28 days. The doses were escalated to receive either 0.25 mg or 0.5 or 1 mg or 1.5 or 2 mg or 3 mg daily for 28 days.
Measure Participants	29
Mean (Standard Error) [Hour*Nanogram per milliliter]	81.8512 (6.0391)

24. Secondary Outcome

Title	Part 2: Number of Participants With SAEs and Non-SAEs
Description	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth defect, other situations and is associated with liver injury or impaired liver function. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2:GSK2879552 0.25 mg Daily	Part 2:GSK2879552 0.5 mg Daily	Part 2:GSK2879552 1.0 mg Daily	Part 2:GSK2879552 1.5 mg Daily	Part 2: GSK2879552 2.0 mg Daily	Part 2: GSK2879552 3.0 mg Daily	Part 2: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 2: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 2: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants were planned to receive GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants were planned to receive GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	0	0	0	0	0	0	0	0	0

25. Secondary Outcome

Title	Part 2: Number of Participants With DLTs
Description	An event was considered a DLT if it occured within the first 28 days of treatment, and meets one of the following criteria unless it can be clearly established that the event is unrelated to treatment: recurrent Grade 3 anemia after initial transfusion or Grade 3 anemia lasting > 7 days in participants who are not transfused, Grade 4 neutropenia, Grade 3 neutropenia > 7 days duration, febrile neutropenia as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, Grade 3 thrombocytopenia requiring dose reduction, Grade 4 thrombocytopenia lasting > 3 days or of any duration if associated with clinically significant bleeding, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 2 toxicity (at any time during treatment) and treatment delay of 14 days or greater due to unresolved drug-related toxicity. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2:GSK2879552 0.25 mg Daily	Part 2:GSK2879552 0.5 mg Daily	Part 2:GSK2879552 1.0 mg Daily	Part 2:GSK2879552 1.5 mg Daily	Part 2: GSK2879552 2.0 mg Daily	Part 2: GSK2879552 3.0 mg Daily	Part 2: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 2: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 2: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants were planned to receive GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants were planned to receive GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	0	0	0	0	0	0	0	0	0

26. Secondary Outcome

Title	Part 2: Number of Participants With Dose Reduction or Delays
Description	The number of participants who had any dose reduction or delay were planned to be analyzed. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2:GSK2879552 0.25 mg Daily	Part 2:GSK2879552 0.5 mg Daily	Part 2:GSK2879552 1.0 mg Daily	Part 2:GSK2879552 1.5 mg Daily	Part 2: GSK2879552 2.0 mg Daily	Part 2: GSK2879552 3.0 mg Daily	Part 2: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 2: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 2: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants were planned to receive GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants were planned to receive GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	0	0	0	0	0	0	0	0	0

27. Secondary Outcome

Title	Part 2: Number of Participants Withdrawn Due to Toxicities
Description	Participants were planned to be monitored from start of the study till the development of toxicity in Part 2. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2:GSK2879552 0.25 mg Daily	Part 2:GSK2879552 0.5 mg Daily	Part 2:GSK2879552 1.0 mg Daily	Part 2:GSK2879552 1.5 mg Daily	Part 2: GSK2879552 2.0 mg Daily	Part 2: GSK2879552 3.0 mg Daily	Part 2: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 2: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 2: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants were planned to receive GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants were planned to receive GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	0	0	0	0	0	0	0	0	0

28. Secondary Outcome

Title	Part 2: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline
Description	Blood samples were planned to be collected for evaluation of clinical chemistry parameters including potassium, aspartate aminotransferase (AST), total bilirubin, creatinine, ALT, uric acid, glucose, GGT, albumin, sodium, calcium, alkaline phosphatase, and phosphorus inorganic. Baseline value was defined as the most recent, non-missing value from a central laboratory prior to or on the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame	Baseline and up to 2 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2:GSK2879552 0.25 mg Daily	Part 2:GSK2879552 0.5 mg Daily	Part 2:GSK2879552 1.0 mg Daily	Part 2:GSK2879552 1.5 mg Daily	Part 2: GSK2879552 2.0 mg Daily	Part 2: GSK2879552 3.0 mg Daily	Part 2: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 2: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 2: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants were planned to receive GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants were planned to receive GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	0	0	0	0	0	0	0	0	0

29. Secondary Outcome

Title	Part 2: Number of Participants With Change in Hematology Toxicity Grade From Baseline
Description	Blood samples were planned to be collected for the analysis of hematology parameters including hemoglobin, lymphocytes, total neutrophils, platelet count and white blood cell (WBC) count. Baseline value was defined as the most recent, non-missing value from a central laboratory prior to or on the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame	Baseline and up to 2 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2:GSK2879552 0.25 mg Daily	Part 2:GSK2879552 0.5 mg Daily	Part 2:GSK2879552 1.0 mg Daily	Part 2:GSK2879552 1.5 mg Daily	Part 2: GSK2879552 2.0 mg Daily	Part 2: GSK2879552 3.0 mg Daily	Part 2: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 2: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 2: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants were planned to receive GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants were planned to receive GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	0	0	0	0	0	0	0	0	0

30. Secondary Outcome

Title	Part 2:Number of Participants With Critical Changes in Values of Vital Signs in Response to Drug
Description	Vital sign measurement includes SBP, DBP, temperature, respiration rate and heart rate. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2:GSK2879552 0.25 mg Daily	Part 2:GSK2879552 0.5 mg Daily	Part 2:GSK2879552 1.0 mg Daily	Part 2:GSK2879552 1.5 mg Daily	Part 2: GSK2879552 2.0 mg Daily	Part 2: GSK2879552 3.0 mg Daily	Part 2: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 2: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 2: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants were planned to receive GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants were planned to receive GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	0	0	0	0	0	0	0	0	0

31. Secondary Outcome

Title	Part 2: Number of Participants With Abnormal Findings for ECG Parameters
Description	Single measurements of 12-lead ECGs were planned to be obtained in a semi-recumbent or supine position after at least a 5 minutes rest using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2:GSK2879552 0.25 mg Daily	Part 2:GSK2879552 0.5 mg Daily	Part 2:GSK2879552 1.0 mg Daily	Part 2:GSK2879552 1.5 mg Daily	Part 2: GSK2879552 2.0 mg Daily	Part 2: GSK2879552 3.0 mg Daily	Part 2: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 2: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 2: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants were planned to receive GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants were planned to receive GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	0	0	0	0	0	0	0	0	0

32. Secondary Outcome

Title	Part 2: Number of Participants With Abnormal Findings Undergoing Physical Examinations
Description	The complete physical examination includes assessments of the head, eyes, ears, nose, throat, skin, thyroid, neurological, lungs, cardiovascular, abdomen (liver and spleen), lymph nodes and extremities. A brief physical examination includes assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2:GSK2879552 0.25 mg Daily	Part 2:GSK2879552 0.5 mg Daily	Part 2:GSK2879552 1.0 mg Daily	Part 2:GSK2879552 1.5 mg Daily	Part 2: GSK2879552 2.0 mg Daily	Part 2: GSK2879552 3.0 mg Daily	Part 2: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 2: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 2: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants were planned to receive GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants were planned to receive GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	0	0	0	0	0	0	0	0	0

33. Secondary Outcome

Title	Part 2: Clearance Following Administration of GSK2879552
Description	Blood samples were planned to be collected for population pharmacokinetic analysis of GSK2879552 including clearance. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame	Pre-dose, 0.5, and 3 hours post-dose on Day 1; Pre-dose on Day 8; Pre-dose, 0.5 to 1 hour, and 4 to 6 hours on Day 15; Pre-dose at Day 22 and up to every 4 weeks until Week 48

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population. Data was not collected in Part2 as no participant was enrolled in Part2.

Arm/Group Title	Part 2:GSK2879552 0.25 mg Daily	Part 2:GSK2879552 0.5 mg Daily	Part 2:GSK2879552 1.0 mg Daily	Part 2:GSK2879552 1.5 mg Daily	Part 2: GSK2879552 2.0 mg Daily	Part 2: GSK2879552 3.0 mg Daily	Part 2: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 2: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 2: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants were planned to receive GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants were planned to receive GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	0	0	0	0	0	0	0	0	0

34. Secondary Outcome

Title	Part 2: Volume of Distribution Following Administration of GSK2879552
Description	Blood samples were planned to be collected for population pharmacokinetic analysis of GSK2879552 including volume of distribution. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame	Pre-dose, 0.5, and 3 hours post-dose on Day 1; Pre-dose on Day 8; Pre-dose, 0.5 to 1 hour, and 4 to 6 hours on Day 15; Pre-dose at Day 22 and up to every 4 weeks until Week 48

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population. Data was not collected in Part2 as no participant was enrolled in Part2.

Arm/Group Title	Part 2:GSK2879552 0.25 mg Daily	Part 2:GSK2879552 0.5 mg Daily	Part 2:GSK2879552 1.0 mg Daily	Part 2:GSK2879552 1.5 mg Daily	Part 2: GSK2879552 2.0 mg Daily	Part 2: GSK2879552 3.0 mg Daily	Part 2: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 2: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 2: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants were planned to receive GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants were planned to receive GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	0	0	0	0	0	0	0	0	0

35. Secondary Outcome

Title	Part 2: ED50 of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and Dose
Description	The pharmacokinetic/pharmacodynamic relationship of GSK2879552 administered orally was planned to be characterized by linear and/or non-linear mixed effect models. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Percentage change from Baseline was defined as post-dose visit value minus Baseline value, divided by Baseline value and multiplied by 100. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame	Baseline and up to 2 years

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population. Data was not collected in Part2 as no participant was enrolled in Part2.

Arm/Group Title	Part 2 :Participants With Repeat Daily Dosing
Arm/Group Description	Participants with repeat daily dosing were planned to receive GSK2879552 with a starting dose of 0.25 mg once daily for 28 days. The doses were planned to escalate to receive either 0.25 mg or 0.5 or 1 mg or 1.5 or 2 mg or 3 mg daily for 28 days.
Measure Participants	0

36. Secondary Outcome

Title	Part 2: ED50 of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and Cmax
Description	The pharmacokinetic/pharmacodynamic relationship of GSK2879552 administered orally was planned to be characterized by linear and/or non-linear mixed effect models. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Percentage change from Baseline was defined as post-dose visit value minus Baseline value, divided by Baseline value and multiplied by 100. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame	Baseline and up to 2 years

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population. Data was not collected in Part2 as no participant was enrolled in Part2.

Arm/Group Title	Part 2 :Participants With Repeat Daily Dosing
Arm/Group Description	Participants with repeat daily dosing were planned to receive GSK2879552 with a starting dose of 0.25 mg once daily for 28 days. The doses were planned to escalate to receive either 0.25 mg or 0.5 or 1 mg or 1.5 or 2 mg or 3 mg daily for 28 days.
Measure Participants	0

37. Secondary Outcome

Title	Part 2: ED50 of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and AUC (0 to Infinity)
Description	The pharmacokinetic/pharmacodynamic relationship of GSK2879552 administered orally was planned to be characterized by linear and/or non-linear mixed effect models. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Percentage change from Baseline was defined as post-dose visit value minus Baseline value, divided by Baseline value and multiplied by 100. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame	Baseline and Up to 2 years

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population. Data was not collected in Part2 as no participant was enrolled in Part2.

Arm/Group Title	Part 2 :Participants With Repeat Daily Dosing
Arm/Group Description	Participants with repeat daily dosing were planned to receive GSK2879552 with a starting dose of 0.25 mg once daily for 28 days. The doses were planned to escalate to receive either 0.25 mg or 0.5 or 1 mg or 1.5 or 2 mg or 3 mg daily for 28 days.
Measure Participants	0

38. Secondary Outcome

Title	Part 2: Duration of Response
Description	Duration of response for participants is defined as the time from the first documented evidence of a PR or CR until the first documented sign of disease progression or death due to any cause. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2:GSK2879552 0.25 mg Daily	Part 2:GSK2879552 0.5 mg Daily	Part 2:GSK2879552 1.0 mg Daily	Part 2:GSK2879552 1.5 mg Daily	Part 2: GSK2879552 2.0 mg Daily	Part 2: GSK2879552 3.0 mg Daily	Part 2: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 2: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 2: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants were planned to receive GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants were planned to receive GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	0	0	0	0	0	0	0	0	0

39. Secondary Outcome

Title	Part 2: Progression Free Survival (PFS)
Description	PFS is defined as the interval between the first dose of study medication and the earliest date of disease progression or death due to any cause. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2:GSK2879552 0.25 mg Daily	Part 2:GSK2879552 0.5 mg Daily	Part 2:GSK2879552 1.0 mg Daily	Part 2:GSK2879552 1.5 mg Daily	Part 2: GSK2879552 2.0 mg Daily	Part 2: GSK2879552 3.0 mg Daily	Part 2: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 2: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 2: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants were planned to receive GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants were planned to receive GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	0	0	0	0	0	0	0	0	0

40. Secondary Outcome

Title	Part 2: Percentage of Participants Achieving CR and PR
Description	Overall response rate is defined as percentage of participants achieving CR and PR per RECIST version 1.1. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part 2:GSK2879552 0.25 mg Daily	Part 2:GSK2879552 0.5 mg Daily	Part 2:GSK2879552 1.0 mg Daily	Part 2:GSK2879552 1.5 mg Daily	Part 2: GSK2879552 2.0 mg Daily	Part 2: GSK2879552 3.0 mg Daily	Part 2: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 2: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 2: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants were planned to receive GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	Participants were planned to receive GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
Measure Participants	0	0	0	0	0	0	0	0	0

Adverse Events

Time Frame	Serious adverse events (SAEs) and non-SAEs were collected in Part 1 from the start of the study treatment up to median of 7.286 weeks of drug exposure.
Adverse Event Reporting Description	SAEs and non-SAEs were collected in Part 1 from All Treated Population which included all participants who received at least one dose of study treatment. Data were not collected in Part 2 as no participant was enrolled in Part 2.
Arm/Group Title	Part 1:GSK2879552 0.25 mg Daily		Part 1:GSK2879552 0.5 mg Daily		Part 1:GSK2879552 1.0 mg Daily		Part 1:GSK2879552 1.5 mg Daily		Part 1: GSK2879552 2.0 mg Daily		Part 1: GSK2879552 3.0 mg Daily		Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off		Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off		Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off		Part 2:GSK2879552 0.25 mg Daily		Part 2:GSK2879552 0.5 mg Daily		Part 2:GSK2879552 1.0 mg Daily		Part 2:GSK2879552 1.5 mg Daily		Part 2: GSK2879552 2.0 mg Daily		Part 2: GSK2879552 3.0 mg Daily		Part 2: GSK2879552 3.0 mg 4 Days on/3 Days Off		Part 2: GSK2879552 3.0 mg 4 Days on/10 Days Off		Part 2: GSK2879552 4.0 mg 4 Days on/10 Days Off
Arm/Group Description	Participants received GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.		Participants received GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.		Participants received GSK2879552 with a dose of 1.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.		Participants received GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.		Participants received GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.		Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.		Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.		Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.		Participants received GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.		Participants were planned to receive GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.		Participants were planned to receive GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.		Participants were planned to receive GSK2879552 with a dose of 1 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.		Participants were planned to receive GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.		Participants were planned to receive GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.		Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.		Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.		Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.		Participants were planned to receive GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.
All Cause Mortality
	Part 1:GSK2879552 0.25 mg Daily		Part 1:GSK2879552 0.5 mg Daily		Part 1:GSK2879552 1.0 mg Daily		Part 1:GSK2879552 1.5 mg Daily		Part 1: GSK2879552 2.0 mg Daily		Part 1: GSK2879552 3.0 mg Daily		Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off		Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off		Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off		Part 2:GSK2879552 0.25 mg Daily		Part 2:GSK2879552 0.5 mg Daily		Part 2:GSK2879552 1.0 mg Daily		Part 2:GSK2879552 1.5 mg Daily		Part 2: GSK2879552 2.0 mg Daily		Part 2: GSK2879552 3.0 mg Daily		Part 2: GSK2879552 3.0 mg 4 Days on/3 Days Off		Part 2: GSK2879552 3.0 mg 4 Days on/10 Days Off		Part 2: GSK2879552 4.0 mg 4 Days on/10 Days Off
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)		0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/3 (0%)		0/2 (0%)		0/5 (0%)		1/2 (50%)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	Part 1:GSK2879552 0.25 mg Daily		Part 1:GSK2879552 0.5 mg Daily		Part 1:GSK2879552 1.0 mg Daily		Part 1:GSK2879552 1.5 mg Daily		Part 1: GSK2879552 2.0 mg Daily		Part 1: GSK2879552 3.0 mg Daily		Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off		Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off		Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off		Part 2:GSK2879552 0.25 mg Daily		Part 2:GSK2879552 0.5 mg Daily		Part 2:GSK2879552 1.0 mg Daily		Part 2:GSK2879552 1.5 mg Daily		Part 2: GSK2879552 2.0 mg Daily		Part 2: GSK2879552 3.0 mg Daily		Part 2: GSK2879552 3.0 mg 4 Days on/3 Days Off		Part 2: GSK2879552 3.0 mg 4 Days on/10 Days Off		Part 2: GSK2879552 4.0 mg 4 Days on/10 Days Off
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)		0/5 (0%)		2/3 (66.7%)		2/7 (28.6%)		1/3 (33.3%)		0/2 (0%)		2/5 (40%)		2/2 (100%)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)
Cardiac disorders
Atrial fibrillation	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/2 (50%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Myocardial infarction	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/2 (50%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Pericardial effusion	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
General disorders
Asthenia	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Malaise	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Metabolism and nutrition disorders
Tumour lysis syndrome	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/2 (50%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Nervous system disorders
Encephalopathy	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	1/7 (14.3%)	1	1/3 (33.3%)	1	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Other (Not Including Serious) Adverse Events
	Part 1:GSK2879552 0.25 mg Daily		Part 1:GSK2879552 0.5 mg Daily		Part 1:GSK2879552 1.0 mg Daily		Part 1:GSK2879552 1.5 mg Daily		Part 1: GSK2879552 2.0 mg Daily		Part 1: GSK2879552 3.0 mg Daily		Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off		Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off		Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off		Part 2:GSK2879552 0.25 mg Daily		Part 2:GSK2879552 0.5 mg Daily		Part 2:GSK2879552 1.0 mg Daily		Part 2:GSK2879552 1.5 mg Daily		Part 2: GSK2879552 2.0 mg Daily		Part 2: GSK2879552 3.0 mg Daily		Part 2: GSK2879552 3.0 mg 4 Days on/3 Days Off		Part 2: GSK2879552 3.0 mg 4 Days on/10 Days Off		Part 2: GSK2879552 4.0 mg 4 Days on/10 Days Off
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		1/1 (100%)		5/5 (100%)		2/3 (66.7%)		6/7 (85.7%)		3/3 (100%)		2/2 (100%)		5/5 (100%)		1/2 (50%)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)
Blood and lymphatic system disorders
Thrombocytopenia	1/1 (100%)	1	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	5/7 (71.4%)	7	3/3 (100%)	8	1/2 (50%)	2	2/5 (40%)	3	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Anaemia	0/1 (0%)	0	0/1 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	3/7 (42.9%)	3	1/3 (33.3%)	3	1/2 (50%)	1	2/5 (40%)	3	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Neutropenia	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	3/7 (42.9%)	4	1/3 (33.3%)	1	1/2 (50%)	1	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Lymphopenia	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	4	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Cardiac disorders
Atrial fibrillation	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Ear and labyrinth disorders
Vertigo	1/1 (100%)	2	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Gastrointestinal disorders
Constipation	0/1 (0%)	0	1/1 (100%)	1	2/5 (40%)	2	1/3 (33.3%)	1	2/7 (28.6%)	2	0/3 (0%)	0	2/2 (100%)	2	0/5 (0%)	0	1/2 (50%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Nausea	0/1 (0%)	0	1/1 (100%)	1	3/5 (60%)	3	1/3 (33.3%)	1	0/7 (0%)	0	1/3 (33.3%)	2	0/2 (0%)	0	1/5 (20%)	1	1/2 (50%)	2	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Abdominal pain	0/1 (0%)	0	0/1 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	2/3 (66.7%)	2	1/2 (50%)	1	0/5 (0%)	0	1/2 (50%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Abdominal distension	0/1 (0%)	0	0/1 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/2 (50%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Abdominal pain lower	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	1/2 (50%)	1	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Abdominal pain upper	0/1 (0%)	0	0/1 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/2 (50%)	1	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Diarrhoea	0/1 (0%)	0	0/1 (0%)	0	1/5 (20%)	2	0/3 (0%)	0	1/7 (14.3%)	2	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Dysphagia	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Vomiting	0/1 (0%)	0	1/1 (100%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/2 (50%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Gingival bleeding	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Lip dry	0/1 (0%)	0	1/1 (100%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Rectal prolapse	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Stomatitis	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
General disorders
Fatigue	1/1 (100%)	1	0/1 (0%)	0	2/5 (40%)	2	0/3 (0%)	0	2/7 (28.6%)	4	2/3 (66.7%)	2	1/2 (50%)	1	1/5 (20%)	1	1/2 (50%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Asthenia	0/1 (0%)	0	0/1 (0%)	0	3/5 (60%)	3	1/3 (33.3%)	1	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Pyrexia	1/1 (100%)	1	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	2/7 (28.6%)	2	0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Chest pain	0/1 (0%)	0	0/1 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	1/2 (50%)	1	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Chills	0/1 (0%)	0	0/1 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Mucosal inflammation	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Oedema peripheral	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Pain	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Xerosis	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/2 (50%)	1	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Infections and infestations
Bronchitis	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/2 (50%)	2	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Infected bite	1/1 (100%)	1	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Respiratory tract infection	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Injury, poisoning and procedural complications
Contusion	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Investigations
Alanine aminotransferase increased	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0	2/5 (40%)	2	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Aspartate aminotransferase increased	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Gamma-glutamyltransferase increased	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Platelet count decreased	0/1 (0%)	0	0/1 (0%)	0	1/5 (20%)	1	1/3 (33.3%)	1	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
White blood cell count decreased	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	2	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Blood alkaline phosphatase increased	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Blood bilirubin increased	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Blood creatinine increased	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Blood uric acid increased	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Weight decreased	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Metabolism and nutrition disorders
Decreased appetite	0/1 (0%)	0	0/1 (0%)	0	2/5 (40%)	2	0/3 (0%)	0	0/7 (0%)	0	2/3 (66.7%)	2	2/2 (100%)	2	1/5 (20%)	1	1/2 (50%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Hyponatraemia	0/1 (0%)	0	0/1 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0	1/5 (20%)	2	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Hyperkalaemia	0/1 (0%)	0	0/1 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/2 (50%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Acidosis	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/2 (50%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Hyperglycaemia	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Hyperuricaemia	0/1 (0%)	0	1/1 (100%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Hypoalbuminaemia	0/1 (0%)	0	0/1 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Hypokalaemia	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Hypomagnesaemia	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	3	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Musculoskeletal and connective tissue disorders
Back pain	0/1 (0%)	0	0/1 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	1/7 (14.3%)	1	1/3 (33.3%)	1	0/2 (0%)	0	1/5 (20%)	1	1/2 (50%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Neck pain	0/1 (0%)	0	0/1 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	2/2 (100%)	2	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Flank pain	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	1/2 (50%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Musculoskeletal pain	1/1 (100%)	1	0/1 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Pain in extremity	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	2/7 (28.6%)	2	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Arthralgia	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Joint range of motion decreased	1/1 (100%)	1	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Muscular weakness	0/1 (0%)	0	0/1 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Musculoskeletal chest pain	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Myalgia	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/2 (50%)	1	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Nervous system disorders
Dysgeusia	1/1 (100%)	2	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/2 (50%)	1	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Amnesia	0/1 (0%)	0	0/1 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Coordination abnormal	0/1 (0%)	0	0/1 (0%)	0	1/5 (20%)	2	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Dizziness	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	2	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Epilepsy	0/1 (0%)	0	0/1 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Headache	0/1 (0%)	0	0/1 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Lethargy	0/1 (0%)	0	0/1 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Neuropathy peripheral	1/1 (100%)	1	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Presyncope	0/1 (0%)	0	0/1 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Restless legs syndrome	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Somnolence	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Tremor	1/1 (100%)	1	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Psychiatric disorders
Anxiety	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Confusional state	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Depression	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Disorientation	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Renal and urinary disorders
Acute kidney injury	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0	0/5 (0%)	0	1/2 (50%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Dysuria	1/1 (100%)	1	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Reproductive system and breast disorders
Testicular pain	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	1/3 (33.3%)	2	1/2 (50%)	1	0/5 (0%)	0	1/2 (50%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Nasal congestion	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/2 (50%)	1	1/5 (20%)	1	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Productive cough	0/1 (0%)	0	1/1 (100%)	1	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Atelectasis	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/2 (50%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Cough	0/1 (0%)	0	0/1 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Dysphonia	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/2 (50%)	1	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Dyspnoea exertional	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Haemoptysis	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Orthopnoea	1/1 (100%)	1	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Pleural effusion	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/2 (50%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Upper-airway cough syndrome	1/1 (100%)	1	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Skin and subcutaneous tissue disorders
Rash	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	1/2 (50%)	1	1/5 (20%)	1	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Dry skin	0/1 (0%)	0	1/1 (100%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Erythema	0/1 (0%)	0	1/1 (100%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Pruritus	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Rash maculo-papular	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Vascular disorders
Flushing	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Hypertension	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/2 (50%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Hypotension	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/5 (0%)	0	1/2 (50%)	1	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0
Superior vena cava syndrome	0/1 (0%)	0	0/1 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	1/5 (20%)	1	0/2 (0%)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0	0/0 (NaN)	0

Limitations/Caveats

[Not Specified]

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Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.