Trial Outcomes & Findings for A Safety Study of GSK3039294 in Healthy Volunteers and Patients With Systemic Amyloidosis (NCT NCT02603172)

Last Updated: 2019-09-23

Results Overview

An AE is any untoward medical occurrence in a participants or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization clinical chemor prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect and other important medical events judged by the investigator that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention. Safety population consist of all participants who received at least one dose of the study medication.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

23 participants

Primary outcome timeframe

Up to Day 14

Results posted on

2019-09-23

Participant Flow

Participants took part in the study at one investigative site in the United Kingdom from 12-May-2016 to 10-May-2017. The study was terminated due to safety reasons during conduct of Part B (end of Cohort 3) whereas Cohort 4A and 4B were not recruited in Part B and Part C was not initiated.

This was 3 parts study, participants received GSK3039294: single ascending dose in Part A; repeated dose in Part B; repeat dose in systemic amyloidosis in Part C. Participants in Part A also participated in Part B of the study.

Participant milestones

Participant milestones
Measure	GSK3039294 200 mg + GSK3039294 600 mg In Part A Cohort 1, participants received a single dose of GSK3039294 (dose level 1) 200 milligram (mg) capsules, orally, once on Day 1 and stayed in-house until Day 4; followed by washout period from Day 5 to 14; followed by a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg capsules, orally, once on Day 1 in Part A Cohort 2.	GSK3039294 200 mg + GSK3039294 600 mg/GSK3039294 600 mg QD In Part A Cohort 1, participants received a single dose of GSK3039294 (dose level 1) 200 milligram (mg) capsules, orally, once on Day 1 and stayed in-house until Day 4; followed by washout period from Day 5 to 14; followed by a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg capsules, orally, once on Day 1 in Part A Cohort 2. In Part B Cohort 3, participants received GSK3039294 600 mg capsules, orally, under fed condition, once daily (QD) for 7 days.	GSK3039294 600 mg +GSK3039294 1200 mg In Part A Cohort 2, participants received GSK3039294 (dose level 3) 600 mg capsules, orally, once on Day 1, and stayed in-house until Day 4; followed by washout period from Day 5 to 14; followed by a single dose of GSK3039294 (dose level 4) 1200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4.	GSK3039294 600 mg +GSK3039294 1200 mg/GSK3039294 600 mg QD In Part A Cohort 2, participants received GSK3039294 (dose level 3) 600 mg capsules, orally, once on Day 1, and stayed in-house until Day 4; followed by washout period from Day 5 to 14; followed by a single dose of GSK3039294 (dose level 4) 1200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4. In Part B Cohort 3, participants received GSK3039294 600 mg capsules, orally, under fed condition, once daily (QD) for 7 days.	GSK3039294 600 mg QD In Part B Cohort 3, participants received GSK3039294 600 mg capsules, orally, under fed condition, QD for 7 days.
Part A (Approximately 16 Weeks) STARTED	7	1	8	1	0
Part A (Approximately 16 Weeks) COMPLETED	7	1	7	1	0
Part A (Approximately 16 Weeks) NOT COMPLETED	0	0	1	0	0
Part B (Approximately 7 Weeks) STARTED	0	1	0	1	6
Part B (Approximately 7 Weeks) COMPLETED	0	1	0	1	6
Part B (Approximately 7 Weeks) NOT COMPLETED	0	0	0	0	0
Part C (Approximately 13 Weeks) STARTED	0	0	0	0	0
Part C (Approximately 13 Weeks) COMPLETED	0	0	0	0	0
Part C (Approximately 13 Weeks) NOT COMPLETED	0	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	GSK3039294 200 mg + GSK3039294 600 mg In Part A Cohort 1, participants received a single dose of GSK3039294 (dose level 1) 200 milligram (mg) capsules, orally, once on Day 1 and stayed in-house until Day 4; followed by washout period from Day 5 to 14; followed by a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg capsules, orally, once on Day 1 in Part A Cohort 2.	GSK3039294 200 mg + GSK3039294 600 mg/GSK3039294 600 mg QD In Part A Cohort 1, participants received a single dose of GSK3039294 (dose level 1) 200 milligram (mg) capsules, orally, once on Day 1 and stayed in-house until Day 4; followed by washout period from Day 5 to 14; followed by a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg capsules, orally, once on Day 1 in Part A Cohort 2. In Part B Cohort 3, participants received GSK3039294 600 mg capsules, orally, under fed condition, once daily (QD) for 7 days.	GSK3039294 600 mg +GSK3039294 1200 mg In Part A Cohort 2, participants received GSK3039294 (dose level 3) 600 mg capsules, orally, once on Day 1, and stayed in-house until Day 4; followed by washout period from Day 5 to 14; followed by a single dose of GSK3039294 (dose level 4) 1200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4.	GSK3039294 600 mg +GSK3039294 1200 mg/GSK3039294 600 mg QD In Part A Cohort 2, participants received GSK3039294 (dose level 3) 600 mg capsules, orally, once on Day 1, and stayed in-house until Day 4; followed by washout period from Day 5 to 14; followed by a single dose of GSK3039294 (dose level 4) 1200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4. In Part B Cohort 3, participants received GSK3039294 600 mg capsules, orally, under fed condition, once daily (QD) for 7 days.	GSK3039294 600 mg QD In Part B Cohort 3, participants received GSK3039294 600 mg capsules, orally, under fed condition, QD for 7 days.	GSK3039294 (Cohort 4a) Participants were planned to receive repeat dose of GSK3039294 for 21 days in cohort 4a. The dose level was to be adjusted once during the 21 days. Cohort 4a was not initiated due to safety reasons during conduct of Part B (Cohort 3).	GSK3039294 (Cohort 4b) Participants were planned to receive repeat dose of GSK3039294 for 21 days in cohort 4b. The dose level was to be adjusted once during the 21 days. Cohort 4b was not initiated due to safety reasons during conduct of Part B (Cohort 3).	Part C: GSK3039294 Participants were planned to receive repeat dose of GSK3039294 at the predicted optimal clinical dose determined from Part B for a total of 21 days.
Part A (Approximately 16 Weeks) Adverse Event	0	0	1	0	0	0	0	0

Baseline Characteristics

A Safety Study of GSK3039294 in Healthy Volunteers and Patients With Systemic Amyloidosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GSK3039294 200 mg + GSK3039294 600 mg n=7 Participants In Part A Cohort 1, participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4; followed by washout period from Day 5 to 14; followed by a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg capsules, orally, once on Day 1 in Part A Cohort 2.	GSK3039294 200 mg + GSK3039294 600 mg/GSK3039294 600 mg QD n=1 Participants In Part A Cohort 1, participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4; followed by washout period from Day 5 to 14; followed by a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg capsules, orally, once on Day 1 in Part A Cohort 2. In Part B Cohort 3, participants received GSK3039294 600 mg capsules, orally, under fed condition, QD for 7 days.	GSK3039294 600 mg +GSK3039294 1200 mg n=8 Participants In Part A Cohort 2, participants received GSK3039294 (dose level 3) 600 mg capsules, orally, once on Day 1, and stayed in-house until Day 4; followed by washout period from Day 5 to 14; followed by a single dose of GSK3039294 (dose level 4) 1200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4.	GSK3039294 600 mg +GSK3039294 1200 mg/GSK3039294 600 mg QD n=1 Participants In Part A Cohort 2, participants received GSK3039294 (dose level 3) 600 mg capsules, orally, once on Day 1, and stayed in-house until Day 4; followed by washout period from Day 5 to 14; followed by a single dose of GSK3039294 (dose level 4) 1200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4. In Part B Cohort 3, participants received GSK3039294 600 mg capsules, orally, under fed condition, QD for 7 days.	GSK3039294 600 mg QD n=6 Participants In Part B Cohort 3, participants received GSK3039294 600 mg capsules, orally, under fed condition, QD for 7 days.	GSK3039294 (Cohort 4a) Participants were planned to receive repeat dose of GSK3039294 for 21 days in cohort 4a. The dose level was to be adjusted once during the 21 days. Cohort 4a was not initiated due to safety reasons during conduct of Part B (Cohort 3).	GSK3039294 (Cohort 4b) Participants were planned to receive repeat dose of GSK3039294 for 21 days in cohort 4b. The dose level was to be adjusted once during the 21 days. Cohort 4b was not initiated due to safety reasons during conduct of Part B (Cohort 3).	Part C: GSK3039294 Participants were planned to receive repeat dose of GSK3039294 at the predicted optimal clinical dose determined from Part B for a total of 21 days.	Total n=23 Participants Total of all reporting groups
Age, Continuous	42.4 Years STANDARD_DEVIATION 8.48 • n=5 Participants	26.0 Years STANDARD_DEVIATION NA • n=7 Participants	42.1 Years STANDARD_DEVIATION 13.12 • n=5 Participants	38.0 Years STANDARD_DEVIATION NA • n=4 Participants	36.3 Years STANDARD_DEVIATION 7.79 • n=21 Participants	—	—	—	38.2 Years STANDARD_DEVIATION 9.235 • n=6 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	1 Participants n=7 Participants	8 Participants n=5 Participants	1 Participants n=4 Participants	6 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=6 Participants	23 Participants n=6 Participants
Race/Ethnicity, Customized CENTRAL/SOUTH ASIAN HERITAGE	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=6 Participants	1 Participants n=6 Participants
Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=6 Participants	1 Participants n=6 Participants
Race/Ethnicity, Customized WHITE - WHITE/CAUCASIAN/EUROPEAN HERITAGE	6 Participants n=5 Participants	1 Participants n=7 Participants	7 Participants n=5 Participants	1 Participants n=4 Participants	6 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=6 Participants	21 Participants n=6 Participants

PRIMARY outcome

Timeframe: Up to Day 14

Population: Safety population.

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg n=16 Participants Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part A:Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AEs	1 Participants	6 Participants	5 Participants
Part A:Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any SAEs	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Day 1

Population: Safety population.

PCI ranges for the clinical chemistry parameters were as follows : albumin (low: \<0.86 gram \[g\] per liter \[L\]), calcium (low: \<0.91 millimole \[mmol\]/L and high: \>1.06 mmol/L), glucose (low: \<0.71 mmol/L and high: \>1.41 mmol/L), magnesium (low: \<0.63 mmol/L and high: \>1.03 mmol/L), phosphorous (low: \<0.80 mmol/L and high: \>1.14 mmol/L), potassium (low: \<0.86 mmol/L and high: \>1.10 mmol/L), sodium (low: \<0.96 mmol/L and high: \>1.03 mmol/L), and total carbon dioxide (CO2) (low: \<0.86 mmol/L and high: \>1.14 mmol/L).

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg n=16 Participants Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part A: Number of Participants With Emergent Clinical Chemistry by Potentially Clinical Importance (PCI) Criteria Albumin: low	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With Emergent Clinical Chemistry by Potentially Clinical Importance (PCI) Criteria Albumin: high	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With Emergent Clinical Chemistry by Potentially Clinical Importance (PCI) Criteria Calcium: low	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With Emergent Clinical Chemistry by Potentially Clinical Importance (PCI) Criteria Calcium: high	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With Emergent Clinical Chemistry by Potentially Clinical Importance (PCI) Criteria Glucose: low	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With Emergent Clinical Chemistry by Potentially Clinical Importance (PCI) Criteria Glucose: high	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With Emergent Clinical Chemistry by Potentially Clinical Importance (PCI) Criteria Potassium: low	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With Emergent Clinical Chemistry by Potentially Clinical Importance (PCI) Criteria Potassium: high	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With Emergent Clinical Chemistry by Potentially Clinical Importance (PCI) Criteria Sodium: low	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With Emergent Clinical Chemistry by Potentially Clinical Importance (PCI) Criteria Sodium: high	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Day 1

Population: Safety population

PCI ranges for the hematology parameters were as follows: white blood cell (WBC) count (low: \<0.67 10\^9 cells/L and high: \>1.82 10\^9 cells/L), neutrophil count (low: \<0.83 10\^9 cells/L), hemoglobin (high: \>1.03 g/L in male, \>1.13 g/L in female), hemocrit (high: \>1.02 proportion of red blood cell \[RBC\] in blood for male, \>1.17 proportion of RBC in blood for female), platelet count (low: \<0.67 10\^9 cells/L and high: 1.57 10\^9 cells/L), and lymphocytes (low: \<0.81 10\^9 cells/L).

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg n=16 Participants Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part A: Number of Participants With Emergent Hematology by PCI Criteria Hematocrit: low	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With Emergent Hematology by PCI Criteria Hematocrit: high	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With Emergent Hematology by PCI Criteria Hemoglobin: low	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With Emergent Hematology by PCI Criteria Hemoglobin: high	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With Emergent Hematology by PCI Criteria Leukocytes: low	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With Emergent Hematology by PCI Criteria Leukocytes: high	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With Emergent Hematology by PCI Criteria Lymphocytes: low	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With Emergent Hematology by PCI Criteria Lymphocytes: high	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With Emergent Hematology by PCI Criteria Neutrophils: low	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With Emergent Hematology by PCI Criteria Neutrophils: high	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Day 1

Population: Safety population

Urine samples were collected and urinalysis included analysis of specific gravity, potential of hydrogen (pH), glucose, protein, blood, ketones by dipstick. The dipstick test gives results in a semi-quantitative manner.

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg n=16 Participants Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part A: Number of Participants With Abnormal Urinalysis Data by Dipstick	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline (pre-dose) and 15, 30 minutes, 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours post-dose

Population: Safety Population

Triplicate ECG was measured in semi-supine position after 5 minutes (min) rest. A single 12-lead ECG was measured by using ECG machine that automatically measured PR, QRS, QT, and Fridericia's formula (QTcF) intervals. Baseline is defined as the latest available assessment pre the first dose of study drug within each period in Part A. Change from Baseline was calculated as any visit post Baseline value minus Baseline value.

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg n=16 Participants Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) PR interval: 4 hour	-8.3 Millisecond Standard Deviation 6.41	-7.3 Millisecond Standard Deviation 8.22	-7.1 Millisecond Standard Deviation 4.66
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) PR interval: 6 hour	-6.8 Millisecond Standard Deviation 7.04	-7.6 Millisecond Standard Deviation 9.60	-4.0 Millisecond Standard Deviation 6.98
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) PR interval: 8 hour	-5.0 Millisecond Standard Deviation 6.48	-6.1 Millisecond Standard Deviation 8.38	-5.0 Millisecond Standard Deviation 5.27
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) PR interval: 12 hour	-3.8 Millisecond Standard Deviation 7.42	-6.1 Millisecond Standard Deviation 7.77	-4.7 Millisecond Standard Deviation 9.69
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) PR interval: 24 hour	-0.3 Millisecond Standard Deviation 8.72	-2.8 Millisecond Standard Deviation 9.23	-1.5 Millisecond Standard Deviation 6.51
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) PR interval: 15 minutes	0.5 Millisecond Standard Deviation 5.47	0.9 Millisecond Standard Deviation 7.05	-0.3 Millisecond Standard Deviation 3.47
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) PR interval: 30 minutes	-0.3 Millisecond Standard Deviation 6.24	3.1 Millisecond Standard Deviation 5.65	0.2 Millisecond Standard Deviation 5.35
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) PR interval: 1 hour	-2.3 Millisecond Standard Deviation 8.72	3.2 Millisecond Standard Deviation 6.06	0.3 Millisecond Standard Deviation 7.19
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) PR interval: 2 hour	-0.3 Millisecond Standard Deviation 4.82	0.2 Millisecond Standard Deviation 5.50	0.3 Millisecond Standard Deviation 5.42
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) PR interval: 48 hour	4.2 Millisecond Standard Deviation 10.75	0.9 Millisecond Standard Deviation 8.67	1.0 Millisecond Standard Deviation 4.44
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) PR interval: 72 hour	-3.9 Millisecond Standard Deviation 12.95	-1.7 Millisecond Standard Deviation 11.80	-5.3 Millisecond Standard Deviation 5.43
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QRS duration: 15 minutes	-0.0 Millisecond Standard Deviation 2.28	0.9 Millisecond Standard Deviation 3.76	-1.3 Millisecond Standard Deviation 2.25
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QRS duration: 30 minutes	0.7 Millisecond Standard Deviation 1.89	0.9 Millisecond Standard Deviation 2.70	-0.3 Millisecond Standard Deviation 1.63
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QRS duration: 1 hour	0.3 Millisecond Standard Deviation 3.49	0.1 Millisecond Standard Deviation 2.61	-0.1 Millisecond Standard Deviation 1.69
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QRS duration: 2 hour	-0.3 Millisecond Standard Deviation 2.28	0.1 Millisecond Standard Deviation 1.85	-0.6 Millisecond Standard Deviation 3.55
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QRS duration: 4 hour	0.8 Millisecond Standard Deviation 4.12	1.0 Millisecond Standard Deviation 3.83	1.5 Millisecond Standard Deviation 3.32
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QRS duration: 6 hour	-0.6 Millisecond Standard Deviation 2.65	-0.4 Millisecond Standard Deviation 2.59	-1.2 Millisecond Standard Deviation 2.64
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QRS duration: 8 hour	-0.0 Millisecond Standard Deviation 2.71	0.4 Millisecond Standard Deviation 3.26	-0.6 Millisecond Standard Deviation 3.05
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QRS duration: 12 hour	0.7 Millisecond Standard Deviation 2.05	1.0 Millisecond Standard Deviation 4.28	0.9 Millisecond Standard Deviation 3.85
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QRS duration: 24 hour	-0.2 Millisecond Standard Deviation 1.70	0.1 Millisecond Standard Deviation 2.40	-0.5 Millisecond Standard Deviation 2.82
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QRS duration: 48 hour	1.3 Millisecond Standard Deviation 2.57	2.0 Millisecond Standard Deviation 4.18	0.3 Millisecond Standard Deviation 3.79
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QRS duration: 72 hour	0.5 Millisecond Standard Deviation 1.84	2.7 Millisecond Standard Deviation 3.39	-2.0 Millisecond Standard Deviation 4.83
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QT interval: 15 minutes	5.6 Millisecond Standard Deviation 6.72	-2.4 Millisecond Standard Deviation 13.95	-3.0 Millisecond Standard Deviation 5.51
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QT interval: 30 minutes	1.3 Millisecond Standard Deviation 7.81	0.4 Millisecond Standard Deviation 10.44	-2.5 Millisecond Standard Deviation 5.31
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QT interval: 1 hour	4.8 Millisecond Standard Deviation 11.90	3.0 Millisecond Standard Deviation 12.77	-3.8 Millisecond Standard Deviation 8.45
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QT interval: 2 hour	3.2 Millisecond Standard Deviation 7.12	2.4 Millisecond Standard Deviation 9.32	-1.3 Millisecond Standard Deviation 5.20
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QT interval: 4 hour	-19.5 Millisecond Standard Deviation 4.83	-22.5 Millisecond Standard Deviation 10.73	-18.7 Millisecond Standard Deviation 11.62
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QT interval: 6 hour	-17.8 Millisecond Standard Deviation 8.76	-19.2 Millisecond Standard Deviation 12.40	-21.0 Millisecond Standard Deviation 15.15
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QT interval: 8 hour	-11.0 Millisecond Standard Deviation 17.22	-15.8 Millisecond Standard Deviation 10.78	-14.2 Millisecond Standard Deviation 12.45
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QT interval: 12 hour	-6.2 Millisecond Standard Deviation 10.62	-13.1 Millisecond Standard Deviation 13.87	-16.8 Millisecond Standard Deviation 11.77
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QT interval: 24 hour	-3.7 Millisecond Standard Deviation 12.56	-9.5 Millisecond Standard Deviation 8.32	-4.5 Millisecond Standard Deviation 8.43
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QT interval: 48 hour	-8.0 Millisecond Standard Deviation 16.27	-16.4 Millisecond Standard Deviation 10.05	-19.3 Millisecond Standard Deviation 23.78
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QT interval: 72 hour	-26.0 Millisecond Standard Deviation 23.84	-29.6 Millisecond Standard Deviation 14.29	-27.5 Millisecond Standard Deviation 16.36
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QTcF interval: 15 minutes	-0.7 Millisecond Standard Deviation 2.58	1.1 Millisecond Standard Deviation 9.02	-1.5 Millisecond Standard Deviation 6.95
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QTcF interval: 30 minutes	-3.6 Millisecond Standard Deviation 4.56	2.0 Millisecond Standard Deviation 7.54	-0.2 Millisecond Standard Deviation 6.75
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QTcF interval: 1 hour	-0.6 Millisecond Standard Deviation 4.07	1.4 Millisecond Standard Deviation 6.37	0.7 Millisecond Standard Deviation 6.35
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QTcF interval: 2 hour	0.3 Millisecond Standard Deviation 6.54	0.0 Millisecond Standard Deviation 7.53	1.1 Millisecond Standard Deviation 4.99
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QTcF interval: 4 hour	-2.6 Millisecond Standard Deviation 8.50	-0.3 Millisecond Standard Deviation 10.31	1.6 Millisecond Standard Deviation 8.98
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QTcF interval: 6 hour	-5.6 Millisecond Standard Deviation 5.98	-5.2 Millisecond Standard Deviation 8.96	-2.9 Millisecond Standard Deviation 11.44
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QTcF interval: 8 hour	-6.7 Millisecond Standard Deviation 7.28	-5.9 Millisecond Standard Deviation 7.71	-1.7 Millisecond Standard Deviation 8.63
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QTcF interval: 12 hour	-3.6 Millisecond Standard Deviation 7.30	-4.0 Millisecond Standard Deviation 8.64	-1.4 Millisecond Standard Deviation 9.23
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QTcF interval: 24 hour	-5.6 Millisecond Standard Deviation 7.00	-3.0 Millisecond Standard Deviation 5.35	-3.4 Millisecond Standard Deviation 7.88
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QTcF interval: 48 hour	-8.3 Millisecond Standard Deviation 5.56	-5.9 Millisecond Standard Deviation 8.39	-1.8 Millisecond Standard Deviation 14.81
Part A: Mean Change From Baseline in 12-lead Electrocardiogram (ECG) QTcF interval: 72 hour	-10.4 Millisecond Standard Deviation 10.32	-9.6 Millisecond Standard Deviation 10.65	-3.7 Millisecond Standard Deviation 13.01

PRIMARY outcome

Timeframe: Baseline (pre-dose) and 15, 30 minutes, 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours post-dose

Population: Safety population.

Triplicate ECG was measured in semi-supine position after 5 min rest. A single 12-lead ECG was measured by using ECG machine that automatically measures the heart rate. Baseline is defined as the latest available assessment pre the first dose of study drug within each period in Part A. Change from Baseline was calculated as any visit post Baseline value minus Baseline value.

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg n=16 Participants Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part A: Mean Change From Baseline in Heart Rate by 12-lead ECG 15 minutes	-2.1 Beats per minute Standard Deviation 2.90	0.9 Beats per minute Standard Deviation 4.27	0.6 Beats per minute Standard Deviation 1.96
Part A: Mean Change From Baseline in Heart Rate by 12-lead ECG 30 minutes	-2.0 Beats per minute Standard Deviation 3.10	0.9 Beats per minute Standard Deviation 4.64	1.0 Beats per minute Standard Deviation 2.62
Part A: Mean Change From Baseline in Heart Rate by 12-lead ECG 1 hour	-2.0 Beats per minute Standard Deviation 4.95	-0.4 Beats per minute Standard Deviation 3.72	1.8 Beats per minute Standard Deviation 1.77
Part A: Mean Change From Baseline in Heart Rate by 12-lead ECG 2 hour	-1.1 Beats per minute Standard Deviation 3.97	-0.7 Beats per minute Standard Deviation 3.38	1.0 Beats per minute Standard Deviation 2.27
Part A: Mean Change From Baseline in Heart Rate by 12-lead ECG 4 hour	8.1 Beats per minute Standard Deviation 4.13	9.7 Beats per minute Standard Deviation 4.29	8.3 Beats per minute Standard Deviation 5.27
Part A: Mean Change From Baseline in Heart Rate by 12-lead ECG 6 hour	5.8 Beats per minute Standard Deviation 4.21	5.7 Beats per minute Standard Deviation 4.63	7.3 Beats per minute Standard Deviation 3.52
Part A: Mean Change From Baseline in Heart Rate by 12-lead ECG 8 hour	2.4 Beats per minute Standard Deviation 6.67	4.1 Beats per minute Standard Deviation 4.79	5.2 Beats per minute Standard Deviation 5.55
Part A: Mean Change From Baseline in Heart Rate by 12-lead ECG 12 hour	1.1 Beats per minute Standard Deviation 2.17	3.8 Beats per minute Standard Deviation 4.15	6.3 Beats per minute Standard Deviation 2.69
Part A: Mean Change From Baseline in Heart Rate by 12-lead ECG 24 hour	-1.2 Beats per minute Standard Deviation 4.02	2.7 Beats per minute Standard Deviation 3.33	0.4 Beats per minute Standard Deviation 2.08
Part A: Mean Change From Baseline in Heart Rate by 12-lead ECG 48 hour	-0.4 Beats per minute Standard Deviation 6.70	4.3 Beats per minute Standard Deviation 5.74	7.8 Beats per minute Standard Deviation 8.60
Part A: Mean Change From Baseline in Heart Rate by 12-lead ECG 72 hour	6.9 Beats per minute Standard Deviation 6.33	8.8 Beats per minute Standard Deviation 6.74	10.8 Beats per minute Standard Deviation 8.77

PRIMARY outcome

Timeframe: Baseline (pre-dose) and 15, 30 minutes, 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours post-dose

Population: Safety population.

Systolic BP and diastolic BP were measured in semi-supine position after 5 min rest for the participants at indicated time points. Baseline is defined as the latest available assessment pre the first dose of study drug within each period in Part A. Change from Baseline was calculated as any visit post Baseline value minus Baseline value.

Outcome measures

PRIMARY outcome

Timeframe: Baseline (pre-dose) and 15, 30 minutes, 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours post-dose

Population: Safety population.

Pulse rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Baseline is defined as the latest available assessment pre the first dose of study drug within each period in Part A. Change from Baseline was calculated as any visit post Baseline value minus Baseline value.

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg n=16 Participants Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part A: Mean Change From Baseline in Pulse Rate 15 minutes	0.2 Beats per minute Standard Deviation 2.15	-0.4 Beats per minute Standard Deviation 2.25	0.4 Beats per minute Standard Deviation 3.14
Part A: Mean Change From Baseline in Pulse Rate 30 minutes	-0.4 Beats per minute Standard Deviation 3.06	0.5 Beats per minute Standard Deviation 2.17	1.7 Beats per minute Standard Deviation 2.91
Part A: Mean Change From Baseline in Pulse Rate 1 hour	-0.2 Beats per minute Standard Deviation 5.17	0.4 Beats per minute Standard Deviation 3.10	1.3 Beats per minute Standard Deviation 3.51
Part A: Mean Change From Baseline in Pulse Rate 2 hour	-0.7 Beats per minute Standard Deviation 1.76	-0.3 Beats per minute Standard Deviation 5.00	1.5 Beats per minute Standard Deviation 2.36
Part A: Mean Change From Baseline in Pulse Rate 4 hour	9.3 Beats per minute Standard Deviation 4.64	9.0 Beats per minute Standard Deviation 4.90	7.9 Beats per minute Standard Deviation 4.01
Part A: Mean Change From Baseline in Pulse Rate 6 hour	7.1 Beats per minute Standard Deviation 6.71	4.6 Beats per minute Standard Deviation 4.44	7.5 Beats per minute Standard Deviation 3.59
Part A: Mean Change From Baseline in Pulse Rate 8 hour	4.4 Beats per minute Standard Deviation 6.29	4.4 Beats per minute Standard Deviation 5.72	5.0 Beats per minute Standard Deviation 5.61
Part A: Mean Change From Baseline in Pulse Rate 12 hour	2.3 Beats per minute Standard Deviation 3.58	3.8 Beats per minute Standard Deviation 3.82	5.5 Beats per minute Standard Deviation 4.01
Part A: Mean Change From Baseline in Pulse Rate 24 hour	2.1 Beats per minute Standard Deviation 3.93	2.1 Beats per minute Standard Deviation 3.22	1.1 Beats per minute Standard Deviation 3.15
Part A: Mean Change From Baseline in Pulse Rate 48 hour	2.5 Beats per minute Standard Deviation 5.53	4.9 Beats per minute Standard Deviation 5.77	7.9 Beats per minute Standard Deviation 9.99
Part A: Mean Change From Baseline in Pulse Rate 72 hour	9.9 Beats per minute Standard Deviation 7.06	9.8 Beats per minute Standard Deviation 7.47	11.1 Beats per minute Standard Deviation 8.94

PRIMARY outcome

Timeframe: Baseline (pre-dose) and 15, 30 minutes, 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours post-dose

Population: Safety population.

Temperature was measured in semi-supine position after 5 min rest for the participants at indicated time points. Baseline is defined as the latest available assessment pre the first dose of study drug within each period in Part A. Change from Baseline was calculated as any visit post Baseline value minus Baseline value.

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg n=16 Participants Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part A: Mean Change From Baseline in Temperature 15 minutes	-0.18 Celsius Standard Deviation 0.292	-0.00 Celsius Standard Deviation 0.339	0.10 Celsius Standard Deviation 0.239
Part A: Mean Change From Baseline in Temperature 30 minutes	-0.14 Celsius Standard Deviation 0.374	-0.02 Celsius Standard Deviation 0.369	0.09 Celsius Standard Deviation 0.253
Part A: Mean Change From Baseline in Temperature 1 hour	-0.26 Celsius Standard Deviation 0.469	0.09 Celsius Standard Deviation 0.380	0.17 Celsius Standard Deviation 0.255
Part A: Mean Change From Baseline in Temperature 2 hour	-0.06 Celsius Standard Deviation 0.288	0.09 Celsius Standard Deviation 0.278	0.21 Celsius Standard Deviation 0.230
Part A: Mean Change From Baseline in Temperature 4 hour	0.24 Celsius Standard Deviation 0.329	0.27 Celsius Standard Deviation 0.453	0.34 Celsius Standard Deviation 0.350
Part A: Mean Change From Baseline in Temperature 6 hour	0.24 Celsius Standard Deviation 0.250	0.53 Celsius Standard Deviation 0.318	0.45 Celsius Standard Deviation 0.334
Part A: Mean Change From Baseline in Temperature 8 hour	-0.00 Celsius Standard Deviation 0.438	0.37 Celsius Standard Deviation 0.427	0.47 Celsius Standard Deviation 0.381
Part A: Mean Change From Baseline in Temperature 12 hour	0.10 Celsius Standard Deviation 0.463	0.19 Celsius Standard Deviation 0.486	0.36 Celsius Standard Deviation 0.534
Part A: Mean Change From Baseline in Temperature 24 hour	0.09 Celsius Standard Deviation 0.439	0.12 Celsius Standard Deviation 0.276	0.08 Celsius Standard Deviation 0.271
Part A: Mean Change From Baseline in Temperature 48 hour	0.05 Celsius Standard Deviation 0.417	0.13 Celsius Standard Deviation 0.334	0.35 Celsius Standard Deviation 0.233
Part A: Mean Change From Baseline in Temperature 72 hour	0.17 Celsius Standard Deviation 0.413	0.20 Celsius Standard Deviation 0.310	0.43 Celsius Standard Deviation 0.282

PRIMARY outcome

Timeframe: Cohort 3: Up to Day 21; Cohort 4: Up to Day 35

Population: Safety population. Data was not collected as study was terminated, due to safety reasons during conduct of Part B (end of Cohort 3) whereas Cohort 4a and 4b were not recruited in Part B.

An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect and other important medical events judged by the investigator that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention.

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part B:Number of Participants With AEs and SAEs Any AE	7 Participants	—	—
Part B:Number of Participants With AEs and SAEs Any SAE	1 Participants	—	—

PRIMARY outcome

Timeframe: Cohort 3 and 4: Up to Day 3

Population: Safety population. Data was not collected as study was terminated, due to safety reasons during conduct of Part B (end of Cohort 3) whereas Cohort 4a and 4b were not recruited in Part B.

PCI ranges for the clinical chemistry parameters were as follows: albumin (low: \<0.86 g/L), calcium (low: \<0.91 mmol/L and high: \>1.06 mmol/L), glucose (low: \<0.71 mmol/L and high: \>1.41 mmol/L), magnesium (low: \<0.63 mmol/L and high: \>1.03 mmol/L), phosphorous (low: \<0.80 mmol/L and high: \>1.14 mmol/L), potassium (low: \<0.86 mmol/L and high: \>1.10 mmol/L), sodium (low: \<0.96 mmol/L and high: \>1.03 mmol/L), and total CO2 (low: \<0.86 mmol/L and high: \>1.14 mmol/L).

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part B: Number of Participants With Emergent Clinical Chemistry by PCI Criteria Albumin: low	0 Participants	—	—
Part B: Number of Participants With Emergent Clinical Chemistry by PCI Criteria Albumin: high	0 Participants	—	—
Part B: Number of Participants With Emergent Clinical Chemistry by PCI Criteria Calcium: low	0 Participants	—	—
Part B: Number of Participants With Emergent Clinical Chemistry by PCI Criteria Calcium: high	0 Participants	—	—
Part B: Number of Participants With Emergent Clinical Chemistry by PCI Criteria Glucose: low	0 Participants	—	—
Part B: Number of Participants With Emergent Clinical Chemistry by PCI Criteria Glucose: high	0 Participants	—	—
Part B: Number of Participants With Emergent Clinical Chemistry by PCI Criteria Potassium: low	0 Participants	—	—
Part B: Number of Participants With Emergent Clinical Chemistry by PCI Criteria Potassium: high	0 Participants	—	—
Part B: Number of Participants With Emergent Clinical Chemistry by PCI Criteria Sodium: low	0 Participants	—	—
Part B: Number of Participants With Emergent Clinical Chemistry by PCI Criteria Sodium: high	0 Participants	—	—

PRIMARY outcome

Timeframe: Cohort 3 and 4: Up to Day 3

Population: Safety population. Data was not collected as study was terminated, due to safety reasons during conduct of Part B (end of Cohort 3) whereas Cohort 4a and 4b were not recruited in Part B.

PCI ranges for the hematology parameters were as follows: WBC count (low: \<0.67 10\^9 cells/L and high: \>1.82 10\^9 cells/L), neutrophil count (low: \<0.83 10\^9 cells/L), hemoglobin (high: \>1.03 g/L in male, \>1.13 g/L in female), hemocrit (high: \>1.02 proportion of RBC in blood for male, \>1.17 proportion of RBC in blood for female), platelet count (low: \<0.67 10\^9 cells/L and high: 1.57 10\^9 cells/L), and lymphocytes (low: \<0.81 10\^9 cells/L).

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part B: Number of Participants With Emergent Hematology by PCI Criteria Hematocrit: low	0 Participants	—	—
Part B: Number of Participants With Emergent Hematology by PCI Criteria Hematocrit: high	0 Participants	—	—
Part B: Number of Participants With Emergent Hematology by PCI Criteria Hemoglobin: low	0 Participants	—	—
Part B: Number of Participants With Emergent Hematology by PCI Criteria Hemoglobin: high	0 Participants	—	—
Part B: Number of Participants With Emergent Hematology by PCI Criteria Leukocytes: low	0 Participants	—	—
Part B: Number of Participants With Emergent Hematology by PCI Criteria Leukocytes: high	0 Participants	—	—
Part B: Number of Participants With Emergent Hematology by PCI Criteria Lymphocytes: low	0 Participants	—	—
Part B: Number of Participants With Emergent Hematology by PCI Criteria Lymphocytes: high	0 Participants	—	—
Part B: Number of Participants With Emergent Hematology by PCI Criteria Neutrophils: low	1 Participants	—	—
Part B: Number of Participants With Emergent Hematology by PCI Criteria Neutrophils: high	0 Participants	—	—

PRIMARY outcome

Timeframe: Cohort 3 and 4: Up to Day 3

Population: Safety population. Data was not collected as study was terminated, due to safety reasons during conduct of Part B (end of Cohort 3) whereas Cohort 4a and 4b were not recruited in Part B.

Urine samples were collected and urinalysis included analysis of specific gravity, pH, glucose, protein, blood, ketones by dipstick. The dipstick test gives results in a semi-quantitative manner.

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part B: Number of Participants With Abnormal Urinalysis Data by Dipstick	0 Participants	—	—

PRIMARY outcome

Timeframe: Cohort 3: Baseline (pre-dose), Day 1 (1 hour), Days 2, 3, 4, 5, 6, 7 (pre-dose and 1 hour), 8 and 21; Cohort 4: Up to Day 35

Population: Safety population. Data was not collected as study was terminated, due to safety reasons during conduct of Part B (end of Cohort 3) whereas Cohort 4a and 4b were not recruited in Part B.

Triplicate ECG was measured in semi-supine position after 5 minutes rest. A single 12-lead ECG was measured by using ECG machine that automatically measured PR, QRS, QT, and QTcF intervals. Baseline is defined as the latest available assessment pre the first dose of study drug in Part B. Change from Baseline was calculated as any visit post Baseline value minus Baseline value.

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part B: Mean Change From Baseline in 12-lead ECG PR interval- Day 1: 1 hour	3.4 Millisecond Standard Deviation 2.42	—	—
Part B: Mean Change From Baseline in 12-lead ECG PR interval- Day 2: pre-dose	2.8 Millisecond Standard Deviation 10.57	—	—
Part B: Mean Change From Baseline in 12-lead ECG PR interval- Day 2: 1 hour	5.3 Millisecond Standard Deviation 7.73	—	—
Part B: Mean Change From Baseline in 12-lead ECG PR interval- Day 3: pre-dose	5.0 Millisecond Standard Deviation 8.05	—	—
Part B: Mean Change From Baseline in 12-lead ECG PR interval- Day 3: 1 hour	6.1 Millisecond Standard Deviation 2.96	—	—
Part B: Mean Change From Baseline in 12-lead ECG PR interval- Day 4: pre-dose	2.9 Millisecond Standard Deviation 8.21	—	—
Part B: Mean Change From Baseline in 12-lead ECG PR interval- Day 4: 1 hour	6.5 Millisecond Standard Deviation 4.48	—	—
Part B: Mean Change From Baseline in 12-lead ECG PR interval- Day 5: pre-dose	4.5 Millisecond Standard Deviation 6.17	—	—
Part B: Mean Change From Baseline in 12-lead ECG PR interval- Day 5: 1 hour	2.9 Millisecond Standard Deviation 9.50	—	—
Part B: Mean Change From Baseline in 12-lead ECG PR interval- Day 6: pre-dose	4.0 Millisecond Standard Deviation 7.57	—	—
Part B: Mean Change From Baseline in 12-lead ECG PR interval- Day 6: 1 hour	6.8 Millisecond Standard Deviation 6.96	—	—
Part B: Mean Change From Baseline in 12-lead ECG PR interval- Day 7: pre-dose	4.6 Millisecond Standard Deviation 7.26	—	—
Part B: Mean Change From Baseline in 12-lead ECG PR interval- Day 7: 1 hour	6.1 Millisecond Standard Deviation 7.13	—	—
Part B: Mean Change From Baseline in 12-lead ECG PR interval- Day 8	7.3 Millisecond Standard Deviation 7.34	—	—
Part B: Mean Change From Baseline in 12-lead ECG PR interval- Day 21	2.5 Millisecond Standard Deviation 8.38	—	—
Part B: Mean Change From Baseline in 12-lead ECG QRS duration- Day 1: 1 hour	-0.1 Millisecond Standard Deviation 1.78	—	—
Part B: Mean Change From Baseline in 12-lead ECG QRS duration- Day 2: pre-dose	-1.3 Millisecond Standard Deviation 4.22	—	—
Part B: Mean Change From Baseline in 12-lead ECG QRS duration- Day 2: 1 hour	-1.3 Millisecond Standard Deviation 5.95	—	—
Part B: Mean Change From Baseline in 12-lead ECG QRS duration- Day 3: pre-dose	-1.5 Millisecond Standard Deviation 3.29	—	—
Part B: Mean Change From Baseline in 12-lead ECG QRS duration- Day 3: 1 hour	-0.2 Millisecond Standard Deviation 3.42	—	—
Part B: Mean Change From Baseline in 12-lead ECG QRS duration- Day 4: pre-dose	1.8 Millisecond Standard Deviation 13.09	—	—
Part B: Mean Change From Baseline in 12-lead ECG QRS duration- Day 4: 1 hour	-1.1 Millisecond Standard Deviation 4.20	—	—
Part B: Mean Change From Baseline in 12-lead ECG QRS duration- Day 5: pre-dose	-1.4 Millisecond Standard Deviation 5.20	—	—
Part B: Mean Change From Baseline in 12-lead ECG QRS duration- Day 5: 1 hour	0.6 Millisecond Standard Deviation 2.97	—	—
Part B: Mean Change From Baseline in 12-lead ECG QRS duration- Day 6: pre-dose	-1.2 Millisecond Standard Deviation 3.41	—	—
Part B: Mean Change From Baseline in 12-lead ECG QRS duration- Day 6: 1 hour	-0.5 Millisecond Standard Deviation 3.08	—	—
Part B: Mean Change From Baseline in 12-lead ECG QRS duration- Day 7: pre-dose	-1.5 Millisecond Standard Deviation 5.25	—	—
Part B: Mean Change From Baseline in 12-lead ECG QRS duration- Day 7: 1 hour	1.1 Millisecond Standard Deviation 4.22	—	—
Part B: Mean Change From Baseline in 12-lead ECG QRS duration- Day 8	-0.9 Millisecond Standard Deviation 5.61	—	—
Part B: Mean Change From Baseline in 12-lead ECG QRS duration- Day 21	-1.5 Millisecond Standard Deviation 6.16	—	—
Part B: Mean Change From Baseline in 12-lead ECG QT interval- Day 1: 1 hour	6.0 Millisecond Standard Deviation 7.47	—	—
Part B: Mean Change From Baseline in 12-lead ECG QT interval- Day 2: pre-dose	5.9 Millisecond Standard Deviation 7.44	—	—
Part B: Mean Change From Baseline in 12-lead ECG QT interval- Day 2: 1 hour	7.2 Millisecond Standard Deviation 7.44	—	—
Part B: Mean Change From Baseline in 12-lead ECG QT interval- Day 3: pre-dose	1.5 Millisecond Standard Deviation 8.11	—	—
Part B: Mean Change From Baseline in 12-lead ECG QT interval- Day 3: 1 hour	1.0 Millisecond Standard Deviation 12.78	—	—
Part B: Mean Change From Baseline in 12-lead ECG QT interval- Day 4: pre-dose	2.9 Millisecond Standard Deviation 9.68	—	—
Part B: Mean Change From Baseline in 12-lead ECG QT interval- Day 4: 1 hour	0.4 Millisecond Standard Deviation 10.60	—	—
Part B: Mean Change From Baseline in 12-lead ECG QT interval- Day 5: pre-dose	1.2 Millisecond Standard Deviation 7.30	—	—
Part B: Mean Change From Baseline in 12-lead ECG QT interval- Day 5: 1 hour	16.6 Millisecond Standard Deviation 16.04	—	—
Part B: Mean Change From Baseline in 12-lead ECG QT interval- Day 6: pre-dose	7.7 Millisecond Standard Deviation 8.64	—	—
Part B: Mean Change From Baseline in 12-lead ECG QT interval- Day 6: 1 hour	2.0 Millisecond Standard Deviation 6.12	—	—
Part B: Mean Change From Baseline in 12-lead ECG QT interval- Day 7: pre-dose	2.6 Millisecond Standard Deviation 11.46	—	—
Part B: Mean Change From Baseline in 12-lead ECG QT interval- Day 7: 1 hour	2.5 Millisecond Standard Deviation 12.02	—	—
Part B: Mean Change From Baseline in 12-lead ECG QT interval- Day 8	1.7 Millisecond Standard Deviation 8.21	—	—
Part B: Mean Change From Baseline in 12-lead ECG QT interval- Day 21	1.4 Millisecond Standard Deviation 12.59	—	—
Part B: Mean Change From Baseline in 12-lead ECG QTcF interval- Day 1: 1 hour	1.1 Millisecond Standard Deviation 5.77	—	—
Part B: Mean Change From Baseline in 12-lead ECG QTcF interval- Day 2: pre-dose	4.3 Millisecond Standard Deviation 5.00	—	—
Part B: Mean Change From Baseline in 12-lead ECG QTcF interval- Day 2: 1 hour	2.7 Millisecond Standard Deviation 4.13	—	—
Part B: Mean Change From Baseline in 12-lead ECG QTcF interval- Day 3: pre-dose	0.5 Millisecond Standard Deviation 3.80	—	—
Part B: Mean Change From Baseline in 12-lead ECG QTcF interval- Day 3: 1 hour	0.1 Millisecond Standard Deviation 5.71	—	—
Part B: Mean Change From Baseline in 12-lead ECG QTcF interval- Day 4: pre-dose	-1.3 Millisecond Standard Deviation 5.49	—	—
Part B: Mean Change From Baseline in 12-lead ECG QTcF interval- Day 4: 1 hour	-3.8 Millisecond Standard Deviation 4.73	—	—
Part B: Mean Change From Baseline in 12-lead ECG QTcF interval- Day 5: pre-dose	-0.4 Millisecond Standard Deviation 5.82	—	—
Part B: Mean Change From Baseline in 12-lead ECG QTcF interval- Day 5: 1 hour	2.3 Millisecond Standard Deviation 10.37	—	—
Part B: Mean Change From Baseline in 12-lead ECG QTcF interval- Day 6: pre-dose	-2.6 Millisecond Standard Deviation 6.92	—	—
Part B: Mean Change From Baseline in 12-lead ECG QTcF interval- Day 6: 1 hour	-1.0 Millisecond Standard Deviation 6.76	—	—
Part B: Mean Change From Baseline in 12-lead ECG QTcF interval- Day 7: pre-dose	2.4 Millisecond Standard Deviation 5.12	—	—
Part B: Mean Change From Baseline in 12-lead ECG QTcF interval- Day 7: 1 hour	0.9 Millisecond Standard Deviation 3.49	—	—
Part B: Mean Change From Baseline in 12-lead ECG QTcF interval- Day 8	0.7 Millisecond Standard Deviation 6.70	—	—
Part B: Mean Change From Baseline in 12-lead ECG QTcF interval- Day 21	7.1 Millisecond Standard Deviation 6.59	—	—

PRIMARY outcome

Timeframe: Cohort 3: Baseline (pre-dose), Day 1 (1 hour), Days 2, 3, 4, 5, 6, 7 (pre-dose and 1 hour), 8 and 21; Cohort 4: Up to Day 35

Population: Safety population. Data was not collected as study was terminated, due to safety reasons during conduct of Part B (end of Cohort 3) whereas Cohort 4a and 4b were not recruited in Part B.

Triplicate ECG was measured in semi-supine position after 5 min rest. A single 12-lead ECG was measured by using ECG machine that automatically measures heart rate. Baseline is defined as the latest available assessment pre the first dose of study drug within each period in Part B. Change from Baseline was calculated as any visit post Baseline value minus Baseline value.

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part B: Mean Change From Baseline in Heart Rate by 12-lead ECG Day 7: 1 hour	-0.6 Beats per minute Standard Deviation 5.92	—	—
Part B: Mean Change From Baseline in Heart Rate by 12-lead ECG Day 8	1.5 Beats per minute Standard Deviation 5.24	—	—
Part B: Mean Change From Baseline in Heart Rate by 12-lead ECG Day 21	3.4 Beats per minute Standard Deviation 8.59	—	—
Part B: Mean Change From Baseline in Heart Rate by 12-lead ECG Day 1: 1 hour	-1.9 Beats per minute Standard Deviation 3.92	—	—
Part B: Mean Change From Baseline in Heart Rate by 12-lead ECG Day 2: pre-dose	-0.6 Beats per minute Standard Deviation 4.27	—	—
Part B: Mean Change From Baseline in Heart Rate by 12-lead ECG Day 2: 1 hour	-2.1 Beats per minute Standard Deviation 3.94	—	—
Part B: Mean Change From Baseline in Heart Rate by 12-lead ECG Day 3: pre-dose	1.3 Beats per minute Standard Deviation 4.84	—	—
Part B: Mean Change From Baseline in Heart Rate by 12-lead ECG Day 3: 1 hour	-0.4 Beats per minute Standard Deviation 4.72	—	—
Part B: Mean Change From Baseline in Heart Rate by 12-lead ECG Day 4: pre-dose	0.9 Beats per minute Standard Deviation 4.20	—	—
Part B: Mean Change From Baseline in Heart Rate by 12-lead ECG Day 4: 1 hour	-1.7 Beats per minute Standard Deviation 3.65	—	—
Part B: Mean Change From Baseline in Heart Rate by 12-lead ECG Day 5: pre-dose	-0.6 Beats per minute Standard Deviation 3.97	—	—
Part B: Mean Change From Baseline in Heart Rate by 12-lead ECG Day 5: 1 hour	9.9 Beats per minute Standard Deviation 6.62	—	—
Part B: Mean Change From Baseline in Heart Rate by 12-lead ECG Day 6: pre-dose	2.4 Beats per minute Standard Deviation 4.59	—	—
Part B: Mean Change From Baseline in Heart Rate by 12-lead ECG Day 6: 1 hour	-1.0 Beats per minute Standard Deviation 4.78	—	—
Part B: Mean Change From Baseline in Heart Rate by 12-lead ECG Day 7: pre-dose	-0.0 Beats per minute Standard Deviation 5.14	—	—

PRIMARY outcome

Timeframe: Cohort 3: Up to Day 8

Population: Safety population.

The cardiac monitoring was measured by using an appropriate nonimplantable recording device which is acceptable to the participants. This was evaluated the arrhythmic background of eligible cardiac amyloidosis participants such that false positive attribution of arrhythmias to GSK3039294 during repeat dosing was minimized.

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part B: Number of Participants With Abnormal Cardiac Telemetry Findings	1 Participants	—	—

PRIMARY outcome

Timeframe: Up to Day 63

Population: Safety Population. Data was not collected as study was terminated due to safety reasons during conduct of Part B (end of Cohort 3) whereas Part C was not initiated.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Up to Day 63

Population: Safety Population. Data was not collected as study was terminated due to safety reasons during conduct of Part B (end of Cohort 3) whereas Part C was not initiated.

PCI parameters for the clinical chemistry that were planned for analysis are as follows: albumin, calcium, glucose, magnesium, phosphorous , potassium , sodium , and total CO2. This analysis was planned but not performed for Part C as the study was terminated early during Part B.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Up to Day 63

Population: Safety Population. Data was not collected as study was terminated due to safety reasons during conduct of Part B (end of Cohort 3) whereas Part C was not initiated.

Hematology parameters that were planned for analysis were as follows: WBC count , neutrophil count , hemoglobin , hemocrit , platelet count , and lymphocytes. This analysis was planned but not performed for Part C as the study was terminated early during Part B.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Up to Day 63

Population: Safety Population. Data was not collected as study was terminated due to safety reasons during conduct of Part B (end of Cohort 3) whereas Part C was not initiated.

Urine samples were planned to be collected and urinalysis included analysis of specific gravity, pH, glucose, protein, blood, ketones by dipstick. This analysis was planned but not performed for Part C as the study was terminated early during Part B.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Up to Day 35

Population: Safety Population. Data was not collected as study was terminated due to safety reasons during conduct of Part B (end of Cohort 3) whereas Part C was not initiated.

Triplicate ECG was planned to be measured in semi-supine position after 5 minutes rest. A single 12-lead ECG was measured by using ECG machine that automatically measured PR, QRS, QT, and QTcF intervals. Baseline is defined as the latest available assessment pre the first dose of study drug within each period in Part C. Change from Baseline was calculated as any visit post Baseline value minus Baseline value. This analysis was planned but not performed for Part C as the study was terminated early during Part B.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Up to Day 35

Population: Safety Population. Data was not collected as study was terminated due to safety reasons during conduct of Part B (end of Cohort 3) whereas Part C was not initiated.

Vital signs included systolic and diastolic BP, pulse rate, heart rate and temperature. This analysis was planned but not performed for Part C as the study was terminated early during Part B.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Up to Day 35

Population: Safety Population. Data was not collected as study was terminated due to safety reasons during conduct of Part B (end of Cohort 3) whereas Part C was not initiated.

The cardiac monitoring was planned to be measured by using an appropriate nonimplantable recording device which is acceptable to the participants. This was evaluated the arrhythmic background of eligible cardiac amyloidosis participants such that false positive attribution of arrhythmias to GSK3039294 during repeat dosing was minimized. This analysis was planned but not performed for Part C as the study was terminated early during Part B.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 and 48 hours post-dose

Population: PK population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Blood samples were collected at specified time points for GSK3039294 and GSK2315698. AUC(0-inf) was determined using standard non-compartmental methods. Pharmacokinetic (PK) population consists of all participants administered at least one dose of study medication and who had at least one PK sample taken and analyzed.

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg n=16 Participants Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part A: Area Under the Concentration-time Curve Extrapolated to Infinity (AUC[0-inf]) of GSK3039294 and GSK2315698 GSK2315698: n= 8, 16, 8	7980.0 Hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 28.17	23432.6 Hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 23.43	41502.4 Hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 14.75

SECONDARY outcome

Timeframe: Pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 and 48 hours post-dose

Population: PK population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Blood samples were collected at specified time points for GSK3039294 and GSK2315698. AUC(0-inf)/D was determined using standard non-compartmental methods.

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg n=16 Participants Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part A: AUC(0-inf) Corrected for Dose of Prodrug (AUC[0-inf]/D) of GSK3039294 and GSK2315698 GSK2315698: n= 8, 16, 8	39.90 h*ng/mL/mg Geometric Coefficient of Variation 28.17	39.05 h*ng/mL/mg Geometric Coefficient of Variation 23.43	34.59 h*ng/mL/mg Geometric Coefficient of Variation 14.75

SECONDARY outcome

Timeframe: Pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 and 48 hours post-dose

Population: PK population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Blood samples were collected at specified time points for GSK3039294 and GSK2315698. AUC(0-t) was determined using standard non-compartmental methods.

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg n=16 Participants Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part A: Area Under the Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-t]) of GSK3039294 and GSK2315698 GSK3039294: n= 0, 9, 4	—	10.03 h*ng/mL Geometric Coefficient of Variation 47.06	18.76 h*ng/mL Geometric Coefficient of Variation 30.31
Part A: Area Under the Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-t]) of GSK3039294 and GSK2315698 GSK2315698: n= 8, 16, 8	7751.0 h*ng/mL Geometric Coefficient of Variation 29.19	23276.5 h*ng/mL Geometric Coefficient of Variation 23.61	41261.4 h*ng/mL Geometric Coefficient of Variation 14.75

SECONDARY outcome

Timeframe: Pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 and 48 hours post-dose

Population: PK population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Blood samples were collected at specified time points for GSK3039294 and GSK2315698. AUC(0-t)/D was determined using standard non-compartmental methods.

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg n=16 Participants Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part A: AUC(0-t) Corrected for Dose of Prodrug (AUC[0-t]/D) of GSK3039294 and GSK2315698 GSK3039294: n= 0, 9, 4	—	0.017 h*ng/mL/mg Geometric Coefficient of Variation 47.06	0.016 h*ng/mL/mg Geometric Coefficient of Variation 30.31
Part A: AUC(0-t) Corrected for Dose of Prodrug (AUC[0-t]/D) of GSK3039294 and GSK2315698 GSK2315698: n= 8, 16, 8	38.75 h*ng/mL/mg Geometric Coefficient of Variation 29.19	38.79 h*ng/mL/mg Geometric Coefficient of Variation 23.61	34.38 h*ng/mL/mg Geometric Coefficient of Variation 14.75

SECONDARY outcome

Timeframe: Pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 and 48 hours post-dose

Population: PK population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). NA indicates that data could not be calculated because only one participant was analyzed.

Blood samples were collected at specified time points for GSK3039294 and GSK2315698. Cmax was determined using standard non-compartmental methods.

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg n=16 Participants Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part A: Maximum Observed Plasma Concentration (Cmax) of GSK3039294 and GSK2315698 GSK3039294: n= 1, 10, 6	30.60 ng/mL Geometric Coefficient of Variation NA NA indicates that data could not be calculated because only one participant was analyzed.	14.82 ng/mL Geometric Coefficient of Variation 18.06	23.62 ng/mL Geometric Coefficient of Variation 56.24
Part A: Maximum Observed Plasma Concentration (Cmax) of GSK3039294 and GSK2315698 GSK2315698: n= 8, 16, 8	3.581 ng/mL Geometric Coefficient of Variation 23.84	3.058 ng/mL Geometric Coefficient of Variation 21.78	2.476 ng/mL Geometric Coefficient of Variation 9.10

SECONDARY outcome

Timeframe: Pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 and 48 hours post-dose

Population: PK population. Data could not be calculated because only one participant was analyzed. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). NA indicates that data could not be calculated because only one participant was analyzed.

Blood samples were collected at specified time points for GSK3039294 and GSK2315698. Cmax/D was determined using standard non-compartmental methods.

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg n=16 Participants Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part A: Cmax Corrected for Dose of Prodrug (Cmax/D) of GSK3039294 and GSK2315698 GSK3039294: n= 1, 10, 6	0.153 ng/mL/mg Geometric Coefficient of Variation NA NA indicates that data could not be calculated because only one participant was analyzed.	0.025 ng/mL/mg Geometric Coefficient of Variation 18.06	0.020 ng/mL/mg Geometric Coefficient of Variation 56.24
Part A: Cmax Corrected for Dose of Prodrug (Cmax/D) of GSK3039294 and GSK2315698 GSK2315698: n= 8, 16, 8	3.581 ng/mL/mg Geometric Coefficient of Variation 23.84	3.058 ng/mL/mg Geometric Coefficient of Variation 21.78	2.476 ng/mL/mg Geometric Coefficient of Variation 9.10

SECONDARY outcome

Timeframe: Pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 and 48 hours post-dose

Population: PK population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Blood samples were collected at specified time points for GSK3039294 and GSK2315698. t1/2 was determined using standard non-compartmental methods.

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg n=16 Participants Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part A: Terminal Half-life (t1/2) of GSK3039294 and GSK2315698 GSK2315698: n= 8, 16, 8	5.097 Hours Geometric Coefficient of Variation 29.60	6.093 Hours Geometric Coefficient of Variation 7.43	5.907 Hours Geometric Coefficient of Variation 7.12

SECONDARY outcome

Timeframe: Pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 and 48 hours post-dose

Population: PK population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Blood samples were collected at specified time points for GSK3039294 and GSK2315698. tmax was determined using standard non-compartmental methods.

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg n=16 Participants Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part A: Time to Reach Cmax (Tmax) of GSK3039294 and GSK2315698 GSK3039294: n= 1, 10, 6	0.750 Hours Interval 0.75 to 0.75	0.500 Hours Interval 0.25 to 1.5	0.867 Hours Interval 0.25 to 1.52
Part A: Time to Reach Cmax (Tmax) of GSK3039294 and GSK2315698 GSK2315698: n= 8, 16, 8	5.000 Hours Interval 3.02 to 5.12	6.000 Hours Interval 4.0 to 8.27	6.000 Hours Interval 1.58 to 8.0

SECONDARY outcome

Timeframe: Cohort 3- Day 4 and 5: pre-dose, and 0.5, 1, 2, 3, 4, and 6 hours post-dose; Cohort 4: Day 4 (pre-dose), Day 5 (pre-dose and 0.5, 1, 2, 3, 4, and 6 hours post-dose)

Population: PK population. Data was not collected as study was terminated, due to safety reasons during conduct of Part B (end of Cohort 3) whereas Cohort 4a and 4b were not recruited in Part B. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Blood samples were collected at specified time points for GSK3039294 and GSK2315698. AUC(0-6) was determined using standard non-compartmental methods.

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part B: Area Under the Concentration-time Curve From Time Zero to 6 Hours Post Dose (AUC[0-6]) of GSK3039294 and GSK2315698 GSK2315698: Day 4 (n= 6, 0, 0)	6899.8 h*ng/mL Geometric Coefficient of Variation 19.72	—	—
Part B: Area Under the Concentration-time Curve From Time Zero to 6 Hours Post Dose (AUC[0-6]) of GSK3039294 and GSK2315698 GSK2315698: Day 5 (n= 8, 0, 0)	8900.1 h*ng/mL Geometric Coefficient of Variation 35.27	—	—

SECONDARY outcome

Timeframe: Cohort 3- Day 4 and 5: pre-dose, and 0.5, 1, 2, 3, 4, and 6 hours post-dose; Cohort 4: Day 4 (pre-dose), Day 5 (pre-dose and 0.5, 1, 2, 3, 4, and 6 hours post-dose)

Population: PK population. Data was not collected for Cohort 4a and 4b as study was terminated due to safety reasons during conduct of Part B (end of Cohort 3). Data was not calculated for Cohort 3 as the concentration-time data does not provide an accurate representation of the terminal elimination phase for the drug. Hence, AUC (0-inf) was not derived.

Blood samples were collected at specified time points for GSK3039294 and GSK2315698. AUC(0-inf) was determined using standard non-compartmental methods.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cohort 3- Day 4 and 5: pre-dose, and 0.5, 1, 2, 3, 4, and 6 hours post-dose; Cohort 4: Day 4 (pre-dose), Day 5 (pre-dose and 0.5, 1, 2, 3, 4, and 6 hours post-dose)

Blood samples were collected at specified time points for GSK3039294 and GSK2315698. AUC(0-inf)/D was determined using standard non-compartmental methods.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cohort 3- Day 4 and 5: pre-dose, and 0.5, 1, 2, 3, 4, and 6 hours post-dose; Cohort 4: Day 4 (pre-dose), Day 5 (pre-dose and 0.5, 1, 2, 3, 4, and 6 hours post-dose)

Blood samples were collected at specified time points for GSK3039294 and GSK2315698. AUC(0-t) was determined using standard non-compartmental methods.

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part B: AUC(0-t) of GSK3039294 and GSK2315698 GSK2315698: Day 4 (n= 7, 0, 0)	7571.9 h*ng/mL Geometric Coefficient of Variation 30.12	—	—
Part B: AUC(0-t) of GSK3039294 and GSK2315698 GSK2315698: Day 5 (n= 8, 0, 0)	8900.1 h*ng/mL Geometric Coefficient of Variation 35.27	—	—

SECONDARY outcome

Timeframe: Cohort 3- Day 4 and 5: pre-dose, and 0.5, 1, 2, 3, 4, and 6 hours post-dose; Cohort 4: Day 4 (pre-dose), Day 5 (pre-dose and 0.5, 1, 2, 3, 4, and 6 hours post-dose)

Blood samples were collected at specified time points for GSK3039294 and GSK2315698. AUC(0-t)/D was determined using standard non-compartmental methods.

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part B: AUC(0-t)/D of GSK3039294 and GSK2315698 GSK2315698: Day 4 (n= 7, 0, 0)	12.62 h*ng/mL/mg Geometric Coefficient of Variation 30.12	—	—
Part B: AUC(0-t)/D of GSK3039294 and GSK2315698 GSK2315698: Day 5 (n= 8, 0, 0)	14.83 h*ng/mL/mg Geometric Coefficient of Variation 35.27	—	—

SECONDARY outcome

Timeframe: Cohort 3- Day 4 and 5: pre-dose, and 0.5, 1, 2, 3, 4, and 6 hours post-dose; Cohort 4: Day 4 (pre-dose), Day 5 (pre-dose and 0.5, 1, 2, 3, 4, and 6 hours post-dose)

Blood samples were collected at specified time points for GSK3039294 and GSK2315698. Cmax was determined using standard non-compartmental methods. NA indicates data could not be calculated because only one participant was analyzed.

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part B: Cmax of GSK3039294 and GSK2315698 GSK3039294: Day 4 (n= 3, 0, 0)	15.25 ng/mL Geometric Coefficient of Variation 55.24	—	—
Part B: Cmax of GSK3039294 and GSK2315698 GSK2315698: Day 4 (n= 7, 0, 0)	1789.7 ng/mL Geometric Coefficient of Variation 29.75	—	—
Part B: Cmax of GSK3039294 and GSK2315698 GSK3039294: Day 5 (n= 1, 0, 0)	16.70 ng/mL Geometric Coefficient of Variation NA NA indicates data could not be calculated because only one participant was analyzed.	—	—
Part B: Cmax of GSK3039294 and GSK2315698 GSK2315698: Day 5 (n= 8, 0, 0)	2652.6 ng/mL Geometric Coefficient of Variation 19.81	—	—

SECONDARY outcome

Timeframe: Cohort 3- Day 4 and 5: pre-dose, and 0.5, 1, 2, 3, 4, and 6 hours post-dose; Cohort 4: Day 4 (pre-dose), Day 5 (pre-dose and 0.5, 1, 2, 3, 4, and 6 hours post-dose)

Blood samples were collected at specified time points for GSK3039294 and GSK2315698. Cmax/D was determined using standard non-compartmental methods. NA indicates that, data could not be calculated because only one participant was analyzed.

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part B: Cmax/D of GSK3039294 and GSK2315698 GSK3039294: Day 4 (n= 3, 0, 0)	0.025 ng/mL/mg Geometric Coefficient of Variation 55.24	—	—
Part B: Cmax/D of GSK3039294 and GSK2315698 GSK2315698: Day 4 (n= 7, 0, 0)	2.983 ng/mL/mg Geometric Coefficient of Variation 29.75	—	—
Part B: Cmax/D of GSK3039294 and GSK2315698 GSK3039294: Day 5 (n= 1, 0, 0)	0.028 ng/mL/mg Geometric Coefficient of Variation NA NA indicates that, data could not be calculated because only one participant was analyzed.	—	—
Part B: Cmax/D of GSK3039294 and GSK2315698 GSK2315698: Day 5 (n= 8, 0, 0)	4.421 ng/mL/mg Geometric Coefficient of Variation 19.81	—	—

SECONDARY outcome

Timeframe: Cohort 3- Day 4 and 5: pre-dose, and 0.5, 1, 2, 3, 4, and 6 hours post-dose; Cohort 4: Day 4 (pre-dose), Day 5 (pre-dose and 0.5, 1, 2, 3, 4, and 6 hours post-dose)

Blood samples were collected at specified time points for GSK3039294 and GSK2315698. t1/2 was determined using standard non-compartmental methods.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cohort 3- Day 4 and 5: pre-dose, and 0.5, 1, 2, 3, 4, and 6 hours post-dose; Cohort 4: Day 4 (pre-dose), Day 5 (pre-dose and 0.5, 1, 2, 3, 4, and 6 hours post-dose)

Blood samples were collected at specified time points for GSK3039294 and GSK2315698. tmax was determined using standard non-compartmental methods.

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part B: Tmax of GSK3039294 and GSK2315698 GSK3039294: Day 4 (n= 3, 0, 0)	0.500 Hours Interval 0.48 to 0.5	—	—
Part B: Tmax of GSK3039294 and GSK2315698 GSK2315698: Day 4 (n= 7, 0, 0)	4.00 Hours Interval 4.0 to 5.95	—	—
Part B: Tmax of GSK3039294 and GSK2315698 GSK3039294: Day 5 (n= 1, 0, 0)	0.500 Hours Interval 0.5 to 0.5	—	—
Part B: Tmax of GSK3039294 and GSK2315698 GSK2315698: Day 5 (n= 8, 0, 0)	6.00 Hours Interval 3.98 to 6.0	—	—

SECONDARY outcome

Timeframe: Cohort 3:Days1(pre-dose, 2hour post-dose),2(pre-dose),4(pre-dose),5(pre-dose, 30min,1,2,3,4,6 hours post-dose),7(pre-dose)and 21post-dose;Cohort4:Days1(pre-dose, 2 hour post-dose),2(pre-dose),4(pre-dose), 5(pre-dose, and 2 hours post-dose) and 35post-dose

Population: PD population. Data was not collected as study was terminated, due to safety reasons during conduct of Part B (end of Cohort 3) whereas Cohort 4a and 4b were not recruited in Part B. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Blood samples were collected at specified time points for GSK3039294. Pharmacodynamic (PD) population consist of all participants who received at least one dose of study medication and who also had a baseline measurement and at least one post-treatment PD measure.

Outcome measures

Outcome measures
Measure	Part A: GSK3039294 200 mg n=8 Participants Participants received a single dose of GSK3039294 (dose level 1) 200 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1.	Part A: GSK3039294 600 mg Participants received a single dose of GSK3039294 (dose level 2) 600 mg capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 1. The remaining participants received the same dose of GSK3039294 (dose level 3) 600 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2. A washout period was maintained from Day 5 to 14 between two treatment cohorts.	Part A: GSK3039294 1200 mg Participants received a single dose of GSK3039294 (dose level 4) 1200 mg, capsules, orally, once on Day 1 and stayed in-house until Day 4 in cohort 2.
Part B: Plasma Serum Amyloid P Component (SAP) Level of GSK3039294 Day 1: pre-dose (n=8, 0, 0)	32318.69 ng/mL Standard Deviation 6403.13	—	—
Part B: Plasma Serum Amyloid P Component (SAP) Level of GSK3039294 Day 1: 2 hour (n=8, 0, 0)	4064.37 ng/mL Standard Deviation 761.37	—	—
Part B: Plasma Serum Amyloid P Component (SAP) Level of GSK3039294 Day 2: pre-dose (n=8, 0, 0)	939.83 ng/mL Standard Deviation 555.71	—	—
Part B: Plasma Serum Amyloid P Component (SAP) Level of GSK3039294 Day 4: pre-dose (n=7, 0, 0)	526.49 ng/mL Standard Deviation 303.64	—	—
Part B: Plasma Serum Amyloid P Component (SAP) Level of GSK3039294 Day 5: pre-dose (n=8, 0, 0)	456.28 ng/mL Standard Deviation 173.19	—	—
Part B: Plasma Serum Amyloid P Component (SAP) Level of GSK3039294 Day 5: 30 min (n=7, 0, 0)	506.16 ng/mL Standard Deviation 232.88	—	—
Part B: Plasma Serum Amyloid P Component (SAP) Level of GSK3039294 Day 5: 1 hour (n=8, 0, 0)	458.72 ng/mL Standard Deviation 174.85	—	—
Part B: Plasma Serum Amyloid P Component (SAP) Level of GSK3039294 Day 5: 2 hour (n=7, 0, 0)	449.03 ng/mL Standard Deviation 160.56	—	—
Part B: Plasma Serum Amyloid P Component (SAP) Level of GSK3039294 Day 5: 3 hour (n=8, 0, 0)	366.31 ng/mL Standard Deviation 101.67	—	—
Part B: Plasma Serum Amyloid P Component (SAP) Level of GSK3039294 Day 5: 4 hour (n=7, 0, 0)	347.81 ng/mL Standard Deviation 115.59	—	—
Part B: Plasma Serum Amyloid P Component (SAP) Level of GSK3039294 Day 5: 6 hour (n=8, 0, 0)	264.79 ng/mL Standard Deviation 72.97	—	—
Part B: Plasma Serum Amyloid P Component (SAP) Level of GSK3039294 Day 7: pre-dose (n=8, 0, 0)	508.32 ng/mL Standard Deviation 301.64	—	—
Part B: Plasma Serum Amyloid P Component (SAP) Level of GSK3039294 Day 21 (n=8, 0, 0)	33320.64 ng/mL Standard Deviation 6252.46	—	—

SECONDARY outcome

Timeframe: Day 1 (pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10 and 12 hours post-dose); Day 2 to 20 (pre-dose); Day 21 (pre-dose, and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose; Week 4 and 5