Trial Outcomes & Findings for Study to Investigate Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of GSK2646264 (NCT NCT02424799)

Results Overview

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. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. Safety population comprised of all participants who took at least one dose of study treatment.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

34 participants

Primary outcome timeframe

Up to Day 7

Results posted on

2019-06-21

Participant Flow

This study was conducted from 17-November-2014 to 10-November-2017 at centers two centers in the United Kingdom and two centers in Germany.

92 participants were screened (3 re-screened) of which 58 were screen failures. Hence 34 participants, 17 healthy participants (Part A), 12 participants with cold urticaria (CU, Part B) and 5 participants with chronic spontaneous urticaria (CsU, Part C) were randomized.

Participant milestones

Participant milestones
Measure	Part A-GSK2646264 0.5% and Placebo Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 centimeter (cm) on the volar aspect of the arm which approximated to 0.2% total body surface area (BSA), on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part A-GSK2646264 1% and Placebo Participants received active treatment (1% cream strength) and placebo on Days 1, 2, 3 and 4. On Day 1 and Day 2, participants received treatment to 0.2% BSA; active treatment on one arm and placebo on the other arm. In addition, participants received treatment to another 5% BSA; active to one side of the torso and placebo to the other. On Days 3 and 4, the same treatment to the arms was applied as on Days 1 and 2, but the %BSA of the torso to which treatment was applied to was increased to 10%.	Part B-Placebo CU participants received matching placebo treatment to an area of 10% BSA (5% BSA on each arm, n=1) or 3.5% BSA (spread over the 2 arms, n=2) on Days 1, 2 and 3	Part B GSK2646264 1% CU participants received 1% strength GSK2646264 to an area of 10% BSA (5% BSA on each arm, n=3) or 3% BSA (spread over the 2 arms, n=6) on Days 1, 2 and 3	Part C-Placebo CSU participants received matching placebo treatment to 10% BSA (arms, legs or torso) on Days 1, 4 and 7.	Part C GSK2646264 1% CSU participants received 1% strength GSK2646264 to 10% BSA (arms, legs or torso) on Days 1, 4 and 7.
Part A (Up to Day 11) STARTED	9	8	0	0	0	0
Part A (Up to Day 11) COMPLETED	9	8	0	0	0	0
Part A (Up to Day 11) NOT COMPLETED	0	0	0	0	0	0
Part B (Up to Day 19) STARTED	0	0	3	9	0	0
Part B (Up to Day 19) COMPLETED	0	0	3	9	0	0
Part B (Up to Day 19) NOT COMPLETED	0	0	0	0	0	0
Part C (Up to Day 23) STARTED	0	0	0	0	1	4
Part C (Up to Day 23) COMPLETED	0	0	0	0	1	4
Part C (Up to Day 23) NOT COMPLETED	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study to Investigate Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of GSK2646264

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A-GSK2646264 0.5% and Placebo n=9 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part A-GSK2646264 1% and Placebo n=8 Participants Participants received active treatment (1% cream strength) and placebo on Days 1, 2, 3 and 4. On Day 1 and Day 2, participants received treatment to 0.2% BSA; active treatment on one arm and placebo on the other arm. In addition, participants received treatment to another 5% BSA; active to one side of the torso and placebo to the other. On Days 3 and 4, the same treatment to the arms was applied as on Days 1 and 2, but the %BSA of the torso to which treatment was applied to was increased to 10%.	Part B-Placebo n=3 Participants CU participants received matching placebo treatment to an area of 10% BSA (5% BSA on each arm, n=1) or 3.5% BSA (spread over the 2 arms, n=2) on days 1, 2 and 3.	Part B GSK2646264 1% n=9 Participants CU participants received 1% strength GSK2646264 to an area of 10% BSA (5% BSA on each arm, n=3) or 3% BSA (spread over the 2 arms, n=6) on days 1, 2 and 3.	Part C-Placebo n=1 Participants CSU participants received matching placebo treatment to 10% BSA (arms, legs or torso) on Days 1, 4 and 7.	Part C GSK2646264 1% n=4 Participants CSU participants received 1% strength GSK2646264 to 10% BSA (arms, legs or torso) on Days 1, 4 and 7.	Total n=34 Participants Total of all reporting groups
Age, Continuous	38.0 Years STANDARD_DEVIATION 10.74 • n=39 Participants	38.9 Years STANDARD_DEVIATION 11.54 • n=41 Participants	41.3 Years STANDARD_DEVIATION 10.07 • n=35 Participants	50.7 Years STANDARD_DEVIATION 11.70 • n=31 Participants	24.0 Years STANDARD_DEVIATION NA • n=146 Participants	50.8 Years STANDARD_DEVIATION 12.58 • n=19 Participants	42.9 Years STANDARD_DEVIATION 12.47 • n=147 Participants
Sex: Female, Male Female	2 Participants n=39 Participants	1 Participants n=41 Participants	2 Participants n=35 Participants	7 Participants n=31 Participants	1 Participants n=146 Participants	4 Participants n=19 Participants	17 Participants n=147 Participants
Sex: Female, Male Male	7 Participants n=39 Participants	7 Participants n=41 Participants	1 Participants n=35 Participants	2 Participants n=31 Participants	0 Participants n=146 Participants	0 Participants n=19 Participants	17 Participants n=147 Participants
Race/Ethnicity, Customized White/Caucasian/European Heritage	9 Participants n=39 Participants	8 Participants n=41 Participants	3 Participants n=35 Participants	8 Participants n=31 Participants	0 Participants n=146 Participants	4 Participants n=19 Participants	32 Participants n=147 Participants
Race/Ethnicity, Customized White-Arabic/North African Heritage	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants	1 Participants n=31 Participants	1 Participants n=146 Participants	0 Participants n=19 Participants	2 Participants n=147 Participants

PRIMARY outcome

Timeframe: Up to Day 7

Population: Safety Population

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. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. Safety population comprised of all participants who took at least one dose of study treatment.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=9 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Part A AEs	4 Participants	—	—	—
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Part A SAEs	0 Participants	—	—	—

PRIMARY outcome

Timeframe: Up to Day 11

Population: Safety Population

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. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=8 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Number of Participants With AEs and SAEs Part A AEs	4 Participants	—	—	—
Number of Participants With AEs and SAEs Part A SAEs	0 Participants	—	—	—

PRIMARY outcome

Timeframe: Up to Day 19

Population: Safety Population

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. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. Data is presented according to the percentage BSA as it impacted safety

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=1 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% n=3 Participants CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo n=2 Participants CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% n=6 Participants CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Number of Participants With AEs and SAEs Part B AEs	1 Participants	3 Participants	0 Participants	3 Participants
Number of Participants With AEs and SAEs Part B SAEs	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to Day 23

Population: Safety Population

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. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=1 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% n=4 Participants CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Number of Participants With AEs and SAEs Part C AEs	1 Participants	1 Participants	—	—
Number of Participants With AEs and SAEs Part C SAEs	0 Participants	0 Participants	—	—

PRIMARY outcome

Timeframe: Up to Day 7

Population: Safety Population

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. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. AE and SAE were categorized as mild=an event that was easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities, moderate=an event that was sufficiently discomforting to interfere with normal everyday activities and severe=an event that prevented normal everyday activities.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=9 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Number of Participants With AEs and SAEs Defined by Severity Part A Mild	3 Participants	—	—	—
Number of Participants With AEs and SAEs Defined by Severity Part A Moderate	1 Participants	—	—	—
Number of Participants With AEs and SAEs Defined by Severity Part A Severe	0 Participants	—	—	—

PRIMARY outcome

Timeframe: Up to Day 11

Population: Safety Population

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. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. AE and SAE were categorized as mild=an event that was easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities, moderate=an event that was sufficiently discomforting to interfere with normal everyday activities and severe=an event that prevented normal everyday activities.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=8 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Number of Participants With AEs and SAEs Defined by Severity Part A Mild	3 Participants	—	—	—
Number of Participants With AEs and SAEs Defined by Severity Part A Moderate	1 Participants	—	—	—
Number of Participants With AEs and SAEs Defined by Severity Part A Severe	0 Participants	—	—	—

PRIMARY outcome

Timeframe: Up to 19 days

Population: Safety Population

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. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. AE and SAE were categorized as mild=an event that was easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities, moderate=an event that was sufficiently discomforting to interfere with normal everyday activities and severe=an event that prevented normal everyday activities. Data is presented according to the percentage BSA as it impacted safety

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=1 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% n=3 Participants CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo n=2 Participants CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% n=6 Participants CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Number of Participants With AEs and SAEs Defined by Severity Part B Mild	1 Participants	2 Participants	0 Participants	2 Participants
Number of Participants With AEs and SAEs Defined by Severity Part B Moderate	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With AEs and SAEs Defined by Severity Part B Severe	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 23 days

Population: Safety Population

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. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. AE and SAE were categorized as mild=an event that was easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities, moderate=an event that was sufficiently discomforting to interfere with normal everyday activities and severe=an event that prevented normal everyday activities.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=1 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% n=4 Participants CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Number of Participants With AEs and SAEs Defined by Severity Part C Mild	1 Participants	1 Participants	—	—
Number of Participants With AEs and SAEs Defined by Severity Part C Moderate	0 Participants	0 Participants	—	—
Number of Participants With AEs and SAEs Defined by Severity Part C Severe	0 Participants	0 Participants	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 4 and follow-up (Day 5 to Day 7)

Population: Safety Population

Vital sign heart rate was measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 2, Day 3, Day 4 and follow-up. Baseline was defined as assessments performed at Day 1(pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=9 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Change From Baseline in Vital Sign Parameter Heart Rate for Part A Day 4	3.0 Beats/minute Standard Deviation 7.12	—	—	—
Change From Baseline in Vital Sign Parameter Heart Rate for Part A Day 2 - Pre-dose	0.2 Beats/minute Standard Deviation 5.43	—	—	—
Change From Baseline in Vital Sign Parameter Heart Rate for Part A Day 3 - Pre-dose	0.9 Beats/minute Standard Deviation 6.01	—	—	—
Change From Baseline in Vital Sign Parameter Heart Rate for Part A Follow-up	10.4 Beats/minute Standard Deviation 9.32	—	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (pre-dose), Day 5, Day 6, Day 7, Day 8 and follow-up (Day 9 to Day 11)

Population: Safety Population

Vital sign heart rate was measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (pre-dose), Day 5, Day 6, Day 7, Day 8 and follow-up. Baseline was defined as assessments performed at Day 1(pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=8 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Change From Baseline in Vital Sign Parameter Heart Rate for Part A Day 2 - Pre-dose	-2.1 Beats/minute Standard Deviation 5.99	—	—	—
Change From Baseline in Vital Sign Parameter Heart Rate for Part A Day 3 - Pre-dose	1.0 Beats/minute Standard Deviation 5.53	—	—	—
Change From Baseline in Vital Sign Parameter Heart Rate for Part A Day 4 - Pre-dose	-0.8 Beats/minute Standard Deviation 5.50	—	—	—
Change From Baseline in Vital Sign Parameter Heart Rate for Part A Day 5	-1.9 Beats/minute Standard Deviation 3.91	—	—	—
Change From Baseline in Vital Sign Parameter Heart Rate for Part A Day 6	1.0 Beats/minute Standard Deviation 2.51	—	—	—
Change From Baseline in Vital Sign Parameter Heart Rate for Part A Day 7	2.0 Beats/minute Standard Deviation 4.07	—	—	—
Change From Baseline in Vital Sign Parameter Heart Rate for Part A Day 8	3.9 Beats/minute Standard Deviation 4.61	—	—	—
Change From Baseline in Vital Sign Parameter Heart Rate for Part A Follow-up	8.0 Beats/minute Standard Deviation 8.73	—	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 6, Day 9, Day 12, Day 15 and follow-up (Day 17 to Day 19)

Population: Safety Population

Vital sign heart rate was measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 2 (pre-dose), Day 3 (pre-dose), Day 6, Day 9, Day 12, Day 15 and follow-up. Baseline was defined as assessments performed at Day 1(pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=3 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% n=9 Participants CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Change From Baseline in Vital Sign Parameter Heart Rate for Part B Day 2 - Pre-dose	8.0 Beats/minute Standard Deviation 6.93	-1.1 Beats/minute Standard Deviation 8.07	—	—
Change From Baseline in Vital Sign Parameter Heart Rate for Part B Day 3 - Pre-dose	10.0 Beats/minute Standard Deviation 5.29	-0.9 Beats/minute Standard Deviation 10.73	—	—
Change From Baseline in Vital Sign Parameter Heart Rate for Part B Day 6	4.0 Beats/minute Standard Deviation 4.0	2.9 Beats/minute Standard Deviation 16.10	—	—
Change From Baseline in Vital Sign Parameter Heart Rate for Part B Day 9	14.0 Beats/minute Standard Deviation 3.46	2.6 Beats/minute Standard Deviation 13.39	—	—
Change From Baseline in Vital Sign Parameter Heart Rate for Part B Day 12	16.0 Beats/minute Standard Deviation 10.58	8.0 Beats/minute Standard Deviation 14.70	—	—
Change From Baseline in Vital Sign Parameter Heart Rate for Part B Day 15	19.3 Beats/minute Standard Deviation 11.02	4.9 Beats/minute Standard Deviation 17.41	—	—
Change From Baseline in Vital Sign Parameter Heart Rate for Part B Follow-up	12.0 Beats/minute Standard Deviation 13.86	2.0 Beats/minute Standard Deviation 18.44	—	—

PRIMARY outcome

Timeframe: Baseline and (Day 1 pre-dose), Day 4 (pre-dose), Day 7 (pre-dose), Day 10, Day 15, follow-up (Day 23)

Population: Safety Population

Vital sign heart rate was measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 4 (pre-dose), Day 7 (pre-dose), Day 10, Day 15 and follow-up. Baseline was defined as assessments performed at Day 1(pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=1 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% n=4 Participants CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Change From Baseline in Vital Sign Parameter Heart Rate for Part C Day 4 - Pre-dose	16.0 Beats/minute Standard Deviation NA NA indicates standard deviation could not be calculated as a single participant was analyzed.	4.8 Beats/minute Standard Deviation 3.95	—	—
Change From Baseline in Vital Sign Parameter Heart Rate for Part C Day 7 - Pre-dose	4.0 Beats/minute Standard Deviation NA NA indicates standard deviation could not be calculated as a single participant was analyzed.	2.3 Beats/minute Standard Deviation 5.56	—	—
Change From Baseline in Vital Sign Parameter Heart Rate for Part C Day 10	20.0 Beats/minute Standard Deviation NA NA indicates standard deviation could not be calculated as a single participant was analyzed.	8.5 Beats/minute Standard Deviation 7.72	—	—
Change From Baseline in Vital Sign Parameter Heart Rate for Part C Day 15	20.0 Beats/minute Standard Deviation NA NA indicates standard deviation could not be calculated as a single participant was analyzed.	14.3 Beats/minute Standard Deviation 5.06	—	—
Change From Baseline in Vital Sign Parameter Heart Rate for Part C Follow-up	8.0 Beats/minute Standard Deviation NA NA indicates standard deviation could not be calculated as a single participant was analyzed.	6.0 Beats/minute Standard Deviation 6.73	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 4 and follow-up (Day 5 to Day 7)

Vital signs SBP and DBP were measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 2, Day 3, Day 4 and follow-up. Baseline was defined as assessments performed at Day 1 (pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=9 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Change From Baseline in Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for Part A SBP, Day 2 - Pre-dose	-0.1 millimeters of mercury Standard Deviation 11.21	—	—	—
Change From Baseline in Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for Part A SBP, Day 3 - Pre-dose	-0.9 millimeters of mercury Standard Deviation 7.27	—	—	—
Change From Baseline in Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for Part A SBP, Day 4	-1.1 millimeters of mercury Standard Deviation 9.31	—	—	—
Change From Baseline in Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for Part A SBP, Follow-up	4.1 millimeters of mercury Standard Deviation 11.38	—	—	—
Change From Baseline in Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for Part A DBP, Day 2 - Pre-dose	-0.3 millimeters of mercury Standard Deviation 4.50	—	—	—
Change From Baseline in Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for Part A DBP, Day 3 - Pre-dose	0.6 millimeters of mercury Standard Deviation 6.52	—	—	—
Change From Baseline in Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for Part A DBP, Day 4	2.2 millimeters of mercury Standard Deviation 4.29	—	—	—
Change From Baseline in Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for Part A DBP, Follow-up	4.2 millimeters of mercury Standard Deviation 6.85	—	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (pre-dose), Day 5, Day 6, Day 7, Day 8 and follow-up (Day 9 to Day 11)

Population: Safety Population

Vital signs SBP and DBP were measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (pre-dose), Day 5, Day 6, Day 7, Day 8 and follow-up. Baseline was defined as assessments performed at Day 1 (pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=8 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Change From Baseline in Vital Sign Parameters SBP and DBP for Part A SBP, Day 2 - Pre-dose	1.0 millimeters of mercury Standard Deviation 12.41	—	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part A SBP, Day 3 - Pre-dose	1.8 millimeters of mercury Standard Deviation 7.69	—	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part A SBP, Day 4 - Pre-dose	1.8 millimeters of mercury Standard Deviation 9.27	—	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part A SBP, Day 5	-2.9 millimeters of mercury Standard Deviation 6.83	—	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part A SBP, Day 6	-3.9 millimeters of mercury Standard Deviation 6.40	—	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part A SBP, Day 7	0.3 millimeters of mercury Standard Deviation 5.09	—	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part A SBP, Day 8	-4.4 millimeters of mercury Standard Deviation 11.54	—	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part A SBP, Follow-up	1.5 millimeters of mercury Standard Deviation 4.41	—	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part A DBP, Day 2 - Pre-dose	-4.0 millimeters of mercury Standard Deviation 5.45	—	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part A DBP, Day 3 - Pre-dose	-0.3 millimeters of mercury Standard Deviation 8.68	—	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part A DBP, Day 4 - Pre-dose	-0.6 millimeters of mercury Standard Deviation 8.86	—	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part A DBP, Day 5	-3.8 millimeters of mercury Standard Deviation 8.66	—	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part A DBP, Day 6	-5.0 millimeters of mercury Standard Deviation 7.84	—	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part A DBP, Day 7	-1.1 millimeters of mercury Standard Deviation 7.62	—	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part A DBP, Day 8	-3.6 millimeters of mercury Standard Deviation 4.50	—	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part A DBP, Follow-up	2.0 millimeters of mercury Standard Deviation 7.46	—	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 6, Day 9, Day 12, Day 15 and follow-up (Day 17 to Day 19)

Population: Safety Population

Vital signs SBP and DBP were measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 2 (pre-dose), Day 3 (pre-dose), Day 6, Day 9, Day 12, Day 15 and follow-up. Baseline was defined as assessments performed at Day 1(pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=3 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% n=9 Participants CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Change From Baseline in Vital Sign Parameters SBP and DBP for Part B SBP, Day 2 - Pre-dose	8.3 millimeters of mercury Standard Deviation 2.89	2.0 millimeters of mercury Standard Deviation 6.60	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part B SBP, Day 3 - Pre-dose	-1.7 millimeters of mercury Standard Deviation 2.89	0.6 millimeters of mercury Standard Deviation 8.82	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part B SBP, Day 6	3.3 millimeters of mercury Standard Deviation 2.89	-1.3 millimeters of mercury Standard Deviation 14.82	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part B SBP, Day 9	5.0 millimeters of mercury Standard Deviation 5.00	-2.2 millimeters of mercury Standard Deviation 10.64	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part B SBP, Day 12	0.0 millimeters of mercury Standard Deviation 0.00	1.4 millimeters of mercury Standard Deviation 14.05	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part B SBP, Day 15	8.3 millimeters of mercury Standard Deviation 2.89	-6.7 millimeters of mercury Standard Deviation 11.73	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part B SBP, Follow-up	0.0 millimeters of mercury Standard Deviation 0.00	-3.3 millimeters of mercury Standard Deviation 12.99	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part B DBP, Day 2 - Pre-dose	1.7 millimeters of mercury Standard Deviation 10.41	2.4 millimeters of mercury Standard Deviation 7.50	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part B DBP, Day 3 - Pre-dose	0.0 millimeters of mercury Standard Deviation 8.66	0.8 millimeters of mercury Standard Deviation 11.03	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part B DBP, Day 6	0.0 millimeters of mercury Standard Deviation 10.00	2.4 millimeters of mercury Standard Deviation 14.05	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part B DBP, Day 9	-3.3 millimeters of mercury Standard Deviation 7.64	3.6 millimeters of mercury Standard Deviation 13.60	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part B DBP, Day 12	-3.3 millimeters of mercury Standard Deviation 5.77	3.0 millimeters of mercury Standard Deviation 9.60	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part B DBP, Day 15	-1.7 millimeters of mercury Standard Deviation 11.55	2.4 millimeters of mercury Standard Deviation 9.08	—	—
Change From Baseline in Vital Sign Parameters SBP and DBP for Part B DBP, Follow-up	-1.7 millimeters of mercury Standard Deviation 12.58	3.0 millimeters of mercury Standard Deviation 13.77	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Day 4 (pre-dose), Day 7 (pre-dose), Day 10, Day 15 and follow-up (Day 23)

Population: Safety Population

Vital signs SBP and DBP were measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 4 (pre-dose), Day 7 (pre-dose), Day 10, Day 15 and follow-up. Baseline was defined as assessments performed at Day 1 (pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=1 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% n=4 Participants CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Change From Baseline in Vital Sign SBP and DBP for Part C SBP, Day 4 - Pre-dose	-10.0 millimeters of mercury Standard Deviation NA NA indicates standard deviation could not be calculated as a single participant was analyzed.	-5.5 millimeters of mercury Standard Deviation 12.56	—	—
Change From Baseline in Vital Sign SBP and DBP for Part C SBP, Day 7 - Pre-dose	-10.0 millimeters of mercury Standard Deviation NA NA indicates standard deviation could not be calculated as a single participant was analyzed.	-4.5 millimeters of mercury Standard Deviation 17.60	—	—
Change From Baseline in Vital Sign SBP and DBP for Part C SBP, Day 10	-10.0 millimeters of mercury Standard Deviation NA NA indicates standard deviation could not be calculated as a single participant was analyzed.	5.3 millimeters of mercury Standard Deviation 15.06	—	—
Change From Baseline in Vital Sign SBP and DBP for Part C SBP, Day 15	-10.0 millimeters of mercury Standard Deviation NA NA indicates standard deviation could not be calculated as a single participant was analyzed.	12.3 millimeters of mercury Standard Deviation 28.83	—	—
Change From Baseline in Vital Sign SBP and DBP for Part C SBP, Follow-up	0.0 millimeters of mercury Standard Deviation NA NA indicates standard deviation could not be calculated as a single participant was analyzed.	10.0 millimeters of mercury Standard Deviation 18.55	—	—
Change From Baseline in Vital Sign SBP and DBP for Part C DBP, Day 4 - Pre-dose	-10.0 millimeters of mercury Standard Deviation NA NA indicates standard deviation could not be calculated as a single participant was analyzed.	-5.0 millimeters of mercury Standard Deviation 9.13	—	—
Change From Baseline in Vital Sign SBP and DBP for Part C DBP, Day 7 - Pre-dose	-10.0 millimeters of mercury Standard Deviation NA NA indicates standard deviation could not be calculated as a single participant was analyzed.	-4.8 millimeters of mercury Standard Deviation 8.18	—	—
Change From Baseline in Vital Sign SBP and DBP for Part C DBP, Day 10	-20.0 millimeters of mercury Standard Deviation NA NA indicates standard deviation could not be calculated as a single participant was analyzed.	-6.5 millimeters of mercury Standard Deviation 3.70	—	—
Change From Baseline in Vital Sign SBP and DBP for Part C DBP, Day 15	-10.0 millimeters of mercury Standard Deviation NA NA indicates standard deviation could not be calculated as a single participant was analyzed.	-1.0 millimeters of mercury Standard Deviation 10.89	—	—
Change From Baseline in Vital Sign SBP and DBP for Part C DBP, Follow-up	-10.0 millimeters of mercury Standard Deviation NA NA indicates standard deviation could not be calculated as a single participant was analyzed.	2.0 millimeters of mercury Standard Deviation 2.0	—	—

PRIMARY outcome

Timeframe: Baseline (Day -1) and Day 4, and follow-up (Day 5 to Day 7)

Population: Safety Population

Triplicate 12-lead ECGs were obtained at screening and during the study single ECGs were taken. At each time point during the study ECG was taken using an ECG machine that automatically calculates the heart rate and measured the PR interval, QRS duration, corrected QT (QTc-Bazett \[QTcB\], QTC interval-Fredericia \[QTcF\]) intervals, RR interval and uncorrected QT interval. Baseline was defined as assessment performed at Day -1. Change from Baseline was calculated as the post-dose visit value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=9 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Change From Baseline in Electrocardiogram (ECG) Parameters for Part A PR interval, Day 4	-0.67 milliseconds Standard Deviation 11.136	—	—	—
Change From Baseline in Electrocardiogram (ECG) Parameters for Part A PR interval, Follow-up	0.22 milliseconds Standard Deviation 12.347	—	—	—
Change From Baseline in Electrocardiogram (ECG) Parameters for Part A QRS duration, Day 4	-0.44 milliseconds Standard Deviation 5.637	—	—	—
Change From Baseline in Electrocardiogram (ECG) Parameters for Part A QRS duration, Follow-up	-0.22 milliseconds Standard Deviation 5.239	—	—	—
Change From Baseline in Electrocardiogram (ECG) Parameters for Part A QTcB, Day 4	-6.11 milliseconds Standard Deviation 14.252	—	—	—
Change From Baseline in Electrocardiogram (ECG) Parameters for Part A QTcB, Follow-up	-5.33 milliseconds Standard Deviation 16.963	—	—	—
Change From Baseline in Electrocardiogram (ECG) Parameters for Part A QTcF, Day 4	-1.22 milliseconds Standard Deviation 7.362	—	—	—
Change From Baseline in Electrocardiogram (ECG) Parameters for Part A QTcF, Follow-up	-8.00 milliseconds Standard Deviation 13.829	—	—	—
Change From Baseline in Electrocardiogram (ECG) Parameters for Part A RR interval, Day 4	82.89 milliseconds Standard Deviation 174.628	—	—	—
Change From Baseline in Electrocardiogram (ECG) Parameters for Part A RR interval, Follow-up	-40.11 milliseconds Standard Deviation 114.704	—	—	—
Change From Baseline in Electrocardiogram (ECG) Parameters for Part A Uncorrected QT Interval , Day 4	9.33 milliseconds Standard Deviation 23.302	—	—	—
Change From Baseline in Electrocardiogram (ECG) Parameters for Part A Uncorrected QT Interval , Follow-up	-12.89 milliseconds Standard Deviation 20.028	—	—	—

PRIMARY outcome

Timeframe: Baseline (Day -1) and Day 8 and follow-up (Day 9 to Day 11)

Population: Safety Population

Triplicate 12-lead ECGs were obtained at screening and during the study single ECGs were taken. At each time point during the study ECG was taken using an ECG machine that automatically calculates the heart rate and measured the PR interval, QRS duration, corrected QT (QTc-Bazett \[QTcB\], QTC interval-Fredericia\[QTcF\]) intervals, RR interval and uncorrected QT interval. Baseline was defined as assessment performed at Day -1. Change from Baseline was calculated as the post-dose visit value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=8 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Change From Baseline in Electrocardiogram (ECG) Parameters for Part A PR interval, Day 8	7.75 milliseconds Standard Deviation 17.678	—	—	—
Change From Baseline in Electrocardiogram (ECG) Parameters for Part A PR interval, Follow-up	4.00 milliseconds Standard Deviation 18.237	—	—	—
Change From Baseline in Electrocardiogram (ECG) Parameters for Part A QRS duration, Day 8	0.25 milliseconds Standard Deviation 3.615	—	—	—
Change From Baseline in Electrocardiogram (ECG) Parameters for Part A QRS duration, Follow-up	3.25 milliseconds Standard Deviation 4.132	—	—	—
Change From Baseline in Electrocardiogram (ECG) Parameters for Part A QTcB, Day 8	-5.13 milliseconds Standard Deviation 10.696	—	—	—
Change From Baseline in Electrocardiogram (ECG) Parameters for Part A QTcB, Follow-up	-1.75 milliseconds Standard Deviation 16.211	—	—	—
Change From Baseline in Electrocardiogram (ECG) Parameters for Part A QTcF, Day 8	-4.13 milliseconds Standard Deviation 8.855	—	—	—
Change From Baseline in Electrocardiogram (ECG) Parameters for Part A QTcF, Follow-up	-5.63 milliseconds Standard Deviation 16.309	—	—	—
Change From Baseline in Electrocardiogram (ECG) Parameters for Part A RR interval, Day 8	14.63 milliseconds Standard Deviation 88.569	—	—	—
Change From Baseline in Electrocardiogram (ECG) Parameters for Part A RR interval, Follow-up	-49.75 milliseconds Standard Deviation 98.561	—	—	—
Change From Baseline in Electrocardiogram (ECG) Parameters for Part A Uncorrected QT Interval , Day 8	-2.00 milliseconds Standard Deviation 15.856	—	—	—
Change From Baseline in Electrocardiogram (ECG) Parameters for Part A Uncorrected QT Interval , Follow-up	-13.00 milliseconds Standard Deviation 24.727	—	—	—

PRIMARY outcome

Timeframe: Baseline (Day -1) and Day 3 (pre-dose) and follow-up (Day 17 to Day 19)

Population: Safety Population

Triplicate 12-lead ECGs were obtained at screening and during the study single ECGs were taken. At each time point during the study ECG was taken using an ECG machine that automatically calculates the heart rate and measured the PR interval, QRS duration, QTcB, QTcF intervals, RR interval and uncorrected QT interval. Baseline was defined as assessment performed at Day -1. Change from Baseline was calculated as the post-dose visit value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=3 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% n=9 Participants CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Change From Baseline in ECG Parameters for Part B RR interval, Day 3, Pre-dose	95.33 milliseconds Standard Deviation 74.070	40.56 milliseconds Standard Deviation 131.342	—	—
Change From Baseline in ECG Parameters for Part B QTcF, Day 3, Pre-dose	-6.33 milliseconds Standard Deviation 10.017	-5.00 milliseconds Standard Deviation 11.203	—	—
Change From Baseline in ECG Parameters for Part B RR interval, Follow-up	30.00 milliseconds Standard Deviation 59.355	38.33 milliseconds Standard Deviation 86.510	—	—
Change From Baseline in ECG Parameters for Part B QTcF, Follow-up	-3.00 milliseconds Standard Deviation 20.298	-1.78 milliseconds Standard Deviation 6.906	—	—
Change From Baseline in ECG Parameters for Part B PR interval, Day 3 Pre-dose	-6.67 milliseconds Standard Deviation 5.774	5.56 milliseconds Standard Deviation 10.138	—	—
Change From Baseline in ECG Parameters for Part B PR interval, Follow-up	3.33 milliseconds Standard Deviation 11.547	-2.22 milliseconds Standard Deviation 10.929	—	—
Change From Baseline in ECG Parameters for Part B QRS duration, Day 3 Pre-dose	-6.00 milliseconds Standard Deviation 12.166	-2.44 milliseconds Standard Deviation 2.789	—	—
Change From Baseline in ECG Parameters for Part B QRS duration, Follow-up	-4.67 milliseconds Standard Deviation 8.083	-2.44 milliseconds Standard Deviation 3.127	—	—
Change From Baseline in ECG Parameters for Part B QTcB, Day 3, Pre-dose	-13.00 milliseconds Standard Deviation 6.083	-8.00 milliseconds Standard Deviation 17.428	—	—
Change From Baseline in ECG Parameters for Part B QTcB, Follow-up	-5.33 milliseconds Standard Deviation 21.733	-4.89 milliseconds Standard Deviation 11.185	—	—
Change From Baseline in ECG Parameters for Part B Uncorrected QT Interval , Day 3, Pre-dose	6.67 milliseconds Standard Deviation 19.218	0.67 milliseconds Standard Deviation 17.550	—	—
Change From Baseline in ECG Parameters for Part B Uncorrected QT Interval , Follow-up	1.33 milliseconds Standard Deviation 18.583	3.78 milliseconds Standard Deviation 10.745	—	—

PRIMARY outcome

Timeframe: Baseline (Day -1) and Day 7 (pre-dose) and follow-up (Day 23)

Population: Safety Population

Triplicate 12-lead ECGs were obtained at screening and during the study single ECGs were taken. At each time point during the study ECG was taken using an ECG machine that automatically calculates the heart rate and measured the PR interval, QRS duration, QTcB, QTcF intervals, RR interval and uncorrected QT interval. Baseline was defined as assessment performed at Day -1. Change from Baseline was calculated as the post-dose visit value minus the Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=1 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% n=4 Participants CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Change From Baseline in ECG Parameters for Part C PR interval, Follow-up	-10.00 milliseconds Standard Deviation NA NA indicates standard deviation could not be calculated as a single participant was analyzed.	-3.50 milliseconds Standard Deviation 4.726	—	—
Change From Baseline in ECG Parameters for Part C QTcB, Day 7, Pre-dose	-14.00 milliseconds Standard Deviation NA NA indicates standard deviation could not be calculated as a single participant was analyzed.	-4.50 milliseconds Standard Deviation 5.066	—	—
Change From Baseline in ECG Parameters for Part C PR interval, Day 7 Pre-dose	10.00 milliseconds Standard Deviation NA NA indicates standard deviation could not be calculated as a single participant was analyzed.	1.50 milliseconds Standard Deviation 3.000	—	—
Change From Baseline in ECG Parameters for Part C QRS duration, Day 7 Pre-dose	-14.00 milliseconds Standard Deviation NA NA indicates standard deviation could not be calculated as a single participant was analyzed.	-1.00 milliseconds Standard Deviation 1.155	—	—
Change From Baseline in ECG Parameters for Part C QRS duration, Follow-up	-4.00 milliseconds Standard Deviation NA NA indicates standard deviation could not be calculated as a single participant was analyzed.	0.00 milliseconds Standard Deviation 1.633	—	—
Change From Baseline in ECG Parameters for Part C QTcB, Follow-up	-22.00 milliseconds Standard Deviation NA NA indicates standard deviation could not be calculated as a single participant was analyzed.	9.75 milliseconds Standard Deviation 17.557	—	—
Change From Baseline in ECG Parameters for Part C QTcF, Day 7, Pre-dose	-6.00 milliseconds Standard Deviation NA NA indicates standard deviation could not be calculated as a single participant was analyzed.	-3.25 milliseconds Standard Deviation 6.131	—	—
Change From Baseline in ECG Parameters for Part C QTcF, Follow-up	-11.00 milliseconds Standard Deviation NA NA indicates standard deviation could not be calculated as a single participant was analyzed.	5.75 milliseconds Standard Deviation 12.920	—	—
Change From Baseline in ECG Parameters for Part C RR interval, Day 7, Pre-dose	115.00 milliseconds Standard Deviation NA NA indicates standard deviation could not be calculated as a single participant was analyzed.	17.50 milliseconds Standard Deviation 15.948	—	—
Change From Baseline in ECG Parameters for Part C RR interval, Follow-up	171.00 milliseconds Standard Deviation NA NA indicates standard deviation could not be calculated as a single participant was analyzed.	-35.25 milliseconds Standard Deviation 117.766	—	—
Change From Baseline in ECG Parameters for Part C Uncorrected QT Interval , Day 7, Pre-dose	10.00 milliseconds Standard Deviation NA NA indicates standard deviation could not be calculated as a single participant was analyzed.	-1.00 milliseconds Standard Deviation 7.394	—	—
Change From Baseline in ECG Parameters for Part C Uncorrected QT Interval , Follow-up	12.00 milliseconds Standard Deviation NA NA indicates standard deviation could not be calculated as a single participant was analyzed.	-1.00 milliseconds Standard Deviation 16.452	—	—

PRIMARY outcome

Timeframe: Day 4 and follow up (Day 5 to Day 7)

Population: Safety Population

Clinical chemistry parameters assessed were alanine amino transferase (ALT), albumin (low \<30 grams/liter), alkaline phosphatase, aspartate aminotransferase (AST), calcium (low \<2 millimoles/liter and high \>2.75 millimoles/liter), chloride, creatinine (high \>159 micromoles/liter), direct bilirubin, gamma glutamyl transferase (GGT low \<8 units/liter and high \>78 units/liter), glucose (low \<3 millimoles/liter and high \>11.1 millimoles/liter), phosphorus (low 0.97 millimoles/liter and high 1.45 millimoles/liter), potassium (low \<3 millimoles/liter and high \>5.5 millimoles/liter), sodium (low \<130 millimoles/liter and high \>150 millimoles/liter), total bilirubin, total protein and urea/blood urea nitrogen (BUN). Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=9 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Number of Participants With Clinical Chemistry Data Outside the Range of Potential Clinical Importance (PCI) for Part A	1 Participants	—	—	—

PRIMARY outcome

Timeframe: Day 5, Day 7 and follow up (Day 9 to Day 11)

Population: Safety Population

Clinical chemistry parameters assessed were alanine amino transferase (ALT), albumin (low \<30 grams/liter), alkaline phosphatase, AST, calcium (low \<2 millimoles/liter and high \>2.75 millimoles/liter), chloride, creatinine (high \>159 micromoles/liter), direct bilirubin, GGT (low \<8 units/liter and high \>78 units/liter), glucose (low \<3 millimoles/liter and high \>11.1 millimoles/liter), phosphorus (low 0.97 millimoles/liter and high 1.45 millimoles/liter), potassium (low \<3 millimoles/liter and high \>5.5 millimoles/liter), sodium (low \<130 millimoles/liter and high \>150 millimoles/liter), total bilirubin, total protein and urea/BUN). Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=8 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part A Chloride, Day 5, High	1 Participants	—	—	—
Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part A Chloride, Day 7, High	1 Participants	—	—	—
Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part A Chloride, Follow-up, High,	1 Participants	—	—	—
Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part A GGT, Day 7, Low	1 Participants	—	—	—

PRIMARY outcome

Timeframe: Day 3 and follow up (Day 17 to Day 19)

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

Clinical chemistry parameters assessed were ALT, albumin (low \<30 grams/liter), alkaline phosphatase, AST, calcium (low \<2 millimoles/liter and high \>2.75 millimoles/liter), chloride (low \<98 millimoles/liter and high \>106 millimoles/liter), creatinine (high \>159 micromoles/liter), direct bilirubin, GGT (low \<8 units/liter and high \>78 units/liter), glucose (low \<3 millimoles/liter and high \>11.1 millimoles/liter), phosphorus (low 0.97 millimoles/liter and high 1.45 millimoles/liter), potassium (low \<3 millimoles/liter and high \>5.5 millimoles/liter), sodium (low \<130 millimoles/liter and high \>150 millimoles/liter), total bilirubin, total protein and urea/BUN (low \<2.9 and high \>7.1). Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=3 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% n=9 Participants CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B Direct Bilirubin, Follow-up, High, n=3,9	0 Participants	1 Participants	—	—
Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B Potassium, Follow-up, Low, n=3,9	0 Participants	1 Participants	—	—
Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B Urea/BUN, Follow-up, High, n=3,8	1 Participants	0 Participants	—	—
Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B Chloride, Day 3, Low, n=3,9	1 Participants	1 Participants	—	—
Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B Chloride, Follow up, Low,n=3,9	3 Participants	1 Participants	—	—
Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B Chloride, Follow-up, High, n=3,9	0 Participants	1 Participants	—	—
Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B Direct Bilirubin, Day 3, High, n=3,8	0 Participants	1 Participants	—	—
Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B GGT, Day 3, High, n=3,9	0 Participants	1 Participants	—	—
Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B GGT, Follow-up, Low, n=3,9	1 Participants	0 Participants	—	—
Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B Phosphorus, Day 3, Low, n=3,9	1 Participants	4 Participants	—	—
Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B Phosphorus, Follow-up, Low, n=3,9	1 Participants	3 Participants	—	—
Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B Potassium, Day 3, Low, n=3,9	0 Participants	1 Participants	—	—
Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B Potassium, Day 3, High, n=3,9	1 Participants	0 Participants	—	—
Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B Urea/BUN, Day 3, Low, n=3,9	0 Participants	1 Participants	—	—

PRIMARY outcome

Timeframe: Day 1, Day 7 and follow up (Day 23)

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

Clinical chemistry parameters assessed were ALT, albumin (low \<30 grams/liter), alkaline phosphatase, AST, calcium (low \<2 millimoles/liter and high \>2.75 millimoles/liter), chloride (low \<98 millimoles/liter and high \>106 millimoles/liter), creatinine (high \>159 micromoles/liter), direct bilirubin, GGT (low \<8 units/liter and high \>78 units/liter), glucose (low \<3 millimoles/liter and high \>11.1 millimoles/liter), phosphorus (low 0.97 millimoles/liter and high 1.45 millimoles/liter), potassium (low \<3 millimoles/liter and high \>5.5 millimoles/liter), sodium (low \<130 millimoles/liter and high \>150 millimoles/liter), total bilirubin, total protein (low \<60 grams/liter and high \>78 grams/liter) and urea/BUN (low \<2.9 millimoles/liter and high \>7.1 millimoles/liter). Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=1 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% n=4 Participants CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part C Chloride, Day 7, Low, n=1,2	1 Participants	0 Participants	—	—
Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part C Chloride, Follow-up, Low, n=1,3	0 Participants	1 Participants	—	—
Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part C Phosphorus, Day 1, Low, n=1,4	0 Participants	1 Participants	—	—
Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part C Urea/BUN, Day 1, Low, n=1,2	0 Participants	1 Participants	—	—
Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part C Total protein, Day 1, High, n=1,4	0 Participants	1 Participants	—	—

PRIMARY outcome

Timeframe: Day 4 and follow up (Day 5 to Day 7)

Population: Safety Population

Hematology parameters assessed were basophils (high \>0.1x10\^9 cells/Liter), eosinophils (high \>0.44x 10\^9 cells/Liter), hematocrit, hemoglobin, lymphocytes (low \<0.8x10\^9 cells/Liter), mean corpuscle hemoglobin (MCH low \<28 picograms and high \>32 picograms), mean corpuscle hemoglobin concentration (MCHC low \<32 grams/liter and high \>36 grams/liter), mean corpuscle volume (MCV), monocytes (high \>0.208x 10\^9 cells/Liter), platelet count, red blood cell (RBC low \<4.2x10\^6 cells/microliter and high 5.9x10\^6 cells/microliter) count, total neutrophils and white blood cell (WBC) count. Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=9 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Number of Participants With Hematology Data Outside the Range of PCI for Part A Basophils, Day 4, High	9 Participants	—	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part A Monocytes, Day 4, High	9 Participants	—	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part A Basophils, Follow-up, High	9 Participants	—	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part A Eosinophils, Day 4, High	1 Participants	—	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part A MCH, Day 4, High	1 Participants	—	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part A MCH, Follow-up, High	1 Participants	—	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part A Monocytes, Follow-up, High	9 Participants	—	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part A Lymphocytes, Follow-up, Low	0 Participants	—	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part A RBC count, Follow-up, Low	0 Participants	—	—	—

PRIMARY outcome

Timeframe: Day 5, Day 7 and follow up (Day 9 to Day 11)

Population: Safety Population

Hematology parameters assessed were basophils (high \>0.1x10\^9 cells/Liter), eosinophils (high \>0.44x 10\^9 cells/Liter), hematocrit, hemoglobin, lymphocytes (low \<0.8x10\^9 cells/Liter), MCH (low \<28 picograms and high \>32 picograms), MCHC (low \<32 grams/liter and high \>36 grams/liter), MCV, monocytes (high \>0.208x10\^9 cells/Liter), platelet count, RBC count (low \<4.2x10\^6 cells/microliter and high 5.9x10\^6 cells/microliter) count, total neutrophils, WBC count. Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=8 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Number of Participants With Hematology Data Outside the Range of PCI for Part A Monocytes, Follow-up, High	8 Participants	—	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part A Lymphocytes, Follow-up,Low	1 Participants	—	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part A Basophils, Day 5, High	7 Participants	—	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part A Basophils, Day 7, High	8 Participants	—	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part A Basophils, Follow-up, High	8 Participants	—	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part A MCH, Follow-up, High	0 Participants	—	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part A MCHC, Day 5, High	1 Participants	—	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part A MCHC, Day 7, High	1 Participants	—	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part A Monocytes, Day 5, High	8 Participants	—	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part A Monocytes, Day 7, High	8 Participants	—	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part A RBC count, Day 5, Low	1 Participants	—	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part A RBC count, Day 7, Low	1 Participants	—	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part A RBC count, Follow-up, Low	1 Participants	—	—	—

PRIMARY outcome

Timeframe: Day 3 and follow up (Day 17 to 19)

Population: Safety Population

Hematology parameters assessed were basophils (high \>0.1x10\^9 cells/Liter), eosinophils (high \>0.44x 10\^9 cells/Liter), hematocrit, hemoglobin, lymphocytes (low \<0.8x10\^9 cells/Liter), MCH (low \<28 picograms and high \>32 picograms), MCHC (low \<32 grams/liter and high \>36 grams/liter), MCV, monocytes (high \>0.208x10\^9 cells/Liter), platelet count, RBC count (low \<4.2x10\^6 cells/microliter and high 5.9x10\^6 cells/microliter) count, total neutrophils and WBC count. Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=3 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% n=9 Participants CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Number of Participants With Hematology Data Outside the Range of PCI for Part B RBC count, Follow-up, Low	1 Participants	0 Participants	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part B Basophils, Day 3, High	3 Participants	9 Participants	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part B Basophils, Follow-up, High	3 Participants	9 Participants	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part B Eosinophils, Day 3, High	0 Participants	1 Participants	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part B Eosinophils, Follow-up, High	0 Participants	1 Participants	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part B Monocytes, Day 3, High	3 Participants	9 Participants	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part B Monocytes, Follow-up, High	3 Participants	9 Participants	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part B MCHC, Follow-up, Low	0 Participants	1 Participants	—	—

PRIMARY outcome

Timeframe: Day 1, Day 7 and follow up (Day 23)

Population: Safety Population

Hematology parameters assessed were basophils (high \>0.1x10\^9 cells/Liter), eosinophils (high \>0.44x 10\^9 cells/Liter), hematocrit, hemoglobin, lymphocytes (low \<0.8x10\^9 cells/Liter), MCH (low \<28 picograms and high \>32 picograms), MCHC low \<32 grams/liter and high \>36 grams/liter), MCV, monocytes (high \>0.208x10\^9 cells/Liter), platelet count, RBC count (low \<4.2x10\^6 cells/microliter and high 5.9x10\^6 cells/microliter) count, total neutrophils and WBC count. Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=1 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% n=4 Participants CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Number of Participants With Hematology Data Outside the Range of PCI for Part C Monocytes, Follow-up, High	1 Participants	4 Participants	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part C Basophils, Day 1, High	1 Participants	3 Participants	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part C Basophils, Day 7, High	1 Participants	3 Participants	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part C Basophils, Follow-up, High	1 Participants	2 Participants	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part C Monocytes, Day 1, High	1 Participants	4 Participants	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part C Monocytes, Day 7, High	1 Participants	4 Participants	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part C MCH, Day 1, Low	1 Participants	0 Participants	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part C MCH, Day 7, Low	1 Participants	0 Participants	—	—
Number of Participants With Hematology Data Outside the Range of PCI for Part C MCH, Follow-up, Low	1 Participants	0 Participants	—	—

PRIMARY outcome

Timeframe: Up to Day 4

Population: Safety Population

Tolerability was assessed with the skin irritation scoring system of study, where the score consists of a numeric score according to the dermal response scoring as follows 0=no evidence of irritation, 1=minimal erythema, barely perceptible (pink), 2=moderate erythema (definite redness), 3=strong erythema (intense redness), 4=definite edema, 5=erythema, edema, and papules, 6=vesicular eruption, 7=strong reaction spreading beyond test site, and a letter according to the other effects scoring, Z=no other effect, A=slight glazed appearance, B=marked glazing, C=glazing with peeling and cracking, F=glazing with fissures, G=film of dried serous exudate covering all or part of the patch site, H=small petechial erosions and/or scabs. For each skin assessment, letter grade will be converted to numeric values as below: A=0, Z=0, B=1, C=2, F=3, G=3, H=3. A combined score for each participant was calculated by adding all numeric and letter scores. A maximum score of 3 was allowed.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=9 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% n=9 Participants CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo n=8 Participants CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% n=8 Participants CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Number of Participants With Tolerability Assessment for Part A Maximal dermal response, Grade 4	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Tolerability Assessment for Part A Maximal dermal response, Grade 6	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Tolerability Assessment for Part A Maximal other dermal effects, Z	9 Participants	9 Participants	8 Participants	8 Participants
Number of Participants With Tolerability Assessment for Part A Maximal other dermal effects, F	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Tolerability Assessment for Part A Maximal dermal response, Grade 5	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Tolerability Assessment for Part A Maximal dermal response, Grade 7	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Tolerability Assessment for Part A Maximal other dermal effects, A	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Tolerability Assessment for Part A Maximal other dermal effects, B	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Tolerability Assessment for Part A Maximal other dermal effects, C	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Tolerability Assessment for Part A Maximal other dermal effects, G	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Tolerability Assessment for Part A Maximal other dermal effects, H	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Tolerability Assessment for Part A Maximal dermal response, Grade 0	9 Participants	8 Participants	6 Participants	8 Participants
Number of Participants With Tolerability Assessment for Part A Maximal dermal response, Grade 1	0 Participants	1 Participants	2 Participants	0 Participants
Number of Participants With Tolerability Assessment for Part A Maximal dermal response, Grade 2	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Tolerability Assessment for Part A Maximal dermal response, Grade 3	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to Day 3

Tolerability was assessed with the skin irritation scoring system of study, where the score consists of a numeric score according to the dermal response scoring as follows 0=no evidence of irritation, 1=minimal erythema, barely perceptible (pink), 2=moderate erythema (definite redness), 3=strong erythema (intense redness), 4=definite edema, 5=erythema, edema, and papules, 6=vesicular eruption, 7=strong reaction spreading beyond test site, and a letter according to the other effects scoring, Z=no other effect, A=slight glazed appearance, B=marked glazing, C=glazing with peeling and cracking, F=glazing with fissures, G=film of dried serous exudate covering all or part of the patch site, H=small petechial erosions and/or scabs. For each skin assessment, letter grade will be converted to numeric values as below: A=0, Z=0, B=1, C=2, F=3, G=3, H=3. A combined score for each participant was calculated by adding all numeric and letter scores. A maximum score of 3 was allowed.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=1 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% n=3 Participants CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo n=2 Participants CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% n=6 Participants CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Number of Participants With Tolerability Assessment for Part B Maximal dermal response, Grade 2	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Tolerability Assessment for Part B Maximal dermal response, Grade 5	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Tolerability Assessment for Part B Maximal dermal response, Grade 6	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Tolerability Assessment for Part B Maximal dermal response, Grade 0	0 Participants	0 Participants	2 Participants	6 Participants
Number of Participants With Tolerability Assessment for Part B Maximal dermal response, Grade 1	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Tolerability Assessment for Part B Maximal dermal response, Grade 3	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Tolerability Assessment for Part B Maximal dermal response, Grade 4	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Tolerability Assessment for Part B Maximal dermal response, Grade 7	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Tolerability Assessment for Part B Maximal other dermal effects, Z	1 Participants	2 Participants	2 Participants	6 Participants
Number of Participants With Tolerability Assessment for Part B Maximal other dermal effects, A	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Tolerability Assessment for Part B Maximal other dermal effects, B	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Tolerability Assessment for Part B Maximal other dermal effects, C	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Tolerability Assessment for Part B Maximal other dermal effects, F	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Tolerability Assessment for Part B Maximal other dermal effects, G	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Tolerability Assessment for Part B Maximal other dermal effects, H	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to Day 7

Population: Safety Population

Tolerability was assessed with the skin irritation scoring system of study, where the score consists of a numeric score according to the dermal response scoring as follows 0=no evidence of irritation, 1=minimal erythema, barely perceptible (pink), 2=moderate erythema (definite redness), 3=strong erythema (intense redness), 4=definite edema, 5=erythema, edema, and papules, 6=vesicular eruption, 7=strong reaction spreading beyond test site, and a letter according to the other effects scoring, Z=no other effect, A=slight glazed appearance, B=marked glazing, C=glazing with peeling and cracking, F=glazing with fissures, G=film of dried serous exudate covering all or part of the patch site, H=small petechial erosions and/or scabs. For each skin assessment, letter grade will be converted to numeric values as below: A=0, Z=0, B=1, C=2, F=3, G=3, H=3. A combined score for each participant was calculated by adding all numeric and letter scores. A maximum score of 3 was allowed.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=1 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% n=4 Participants CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Number of Participants With Tolerability Assessment for Part C Maximal dermal response, Grade 4	0 Participants	0 Participants	—	—
Number of Participants With Tolerability Assessment for Part C Maximal dermal response, Grade 0	1 Participants	4 Participants	—	—
Number of Participants With Tolerability Assessment for Part C Maximal dermal response, Grade 1	0 Participants	0 Participants	—	—
Number of Participants With Tolerability Assessment for Part C Maximal dermal response, Grade 2	0 Participants	0 Participants	—	—
Number of Participants With Tolerability Assessment for Part C Maximal dermal response, Grade 3	0 Participants	0 Participants	—	—
Number of Participants With Tolerability Assessment for Part C Maximal dermal response, Grade 5	0 Participants	0 Participants	—	—
Number of Participants With Tolerability Assessment for Part C Maximal dermal response, Grade 6	0 Participants	0 Participants	—	—
Number of Participants With Tolerability Assessment for Part C Maximal dermal response, Grade 7	0 Participants	0 Participants	—	—
Number of Participants With Tolerability Assessment for Part C Maximal other dermal effects, Z	1 Participants	4 Participants	—	—
Number of Participants With Tolerability Assessment for Part C Maximal other dermal effects, A	0 Participants	0 Participants	—	—
Number of Participants With Tolerability Assessment for Part C Maximal other dermal effects, B	0 Participants	0 Participants	—	—
Number of Participants With Tolerability Assessment for Part C Maximal other dermal effects, C	0 Participants	0 Participants	—	—
Number of Participants With Tolerability Assessment for Part C Maximal other dermal effects, F	0 Participants	0 Participants	—	—
Number of Participants With Tolerability Assessment for Part C Maximal other dermal effects, G	0 Participants	0 Participants	—	—
Number of Participants With Tolerability Assessment for Part C Maximal other dermal effects, H	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (1,2,4,8,12,24 hours) and Day 3 (1,2,4,8,12,24 hours)

Population: PK Population

Blood samples were collected to assess the plasma concentration of GSK2646264 for Part A on Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (1,2,4,8,12,24 hours) and Day 3 (1,2,4,8,12,24 hours). The actual date and time of each blood sample collection was recorded. PK Population comprised of all randomized participants of the Safety Population for whom a pharmacokinetic sample was obtained and analyzed.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=9 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 1, Pre-dose	0.00000 nanograms/milliliter Standard Deviation 0.00000	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 1, 1 hour	0.00000 nanograms/milliliter Standard Deviation 0.00000	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 1, 2 hours	0.00000 nanograms/milliliter Standard Deviation 0.00000	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 1, 4 hours	0.00000 nanograms/milliliter Standard Deviation 0.00000	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 1, 8 hours	0.00000 nanograms/milliliter Standard Deviation 0.00000	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 1, 12 hours	0.00708 nanograms/milliliter Standard Deviation 0.021233	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 1, 24 hours	0.02457 nanograms/milliliter Standard Deviation 0.039577	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 2, 1 hour	0.00600 nanograms/milliliter Standard Deviation 0.018000	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 2, 2 hours	0.02524 nanograms/milliliter Standard Deviation 0.038068	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 2, 4 hours	0.07198 nanograms/milliliter Standard Deviation 0.064932	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 2, 8 hours	0.20567 nanograms/milliliter Standard Deviation 0.340281	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 2, 12 hours	0.16524 nanograms/milliliter Standard Deviation 0.117680	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 2, 24 hours	0.23991 nanograms/milliliter Standard Deviation 0.092812	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 3, 1 hour	0.25198 nanograms/milliliter Standard Deviation 0.105292	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 3, 2 hours	0.36364 nanograms/milliliter Standard Deviation 0.197974	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 3, 4 hours	0.50156 nanograms/milliliter Standard Deviation 0.239403	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 3, 8 hours	0.67546 nanograms/milliliter Standard Deviation 0.396632	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 3, 12 hours	0.81486 nanograms/milliliter Standard Deviation 0.463918	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 3, 24 hours	1.03606 nanograms/milliliter Standard Deviation 0.601077	—	—	—

SECONDARY outcome

Timeframe: Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (1,2,4,8,12,24 hours), Day 3 (1,2,4,8,12,24 hours) and Day 4 post-dose at Day 5 (30 and 36 hours), Day 6 (48,54 and 60 hours), Day 7 (72,78 and 84 hours) and Day 8 (96 hours)

Blood samples were collected to assess the plasma concentration of GSK2646264 for Part A on Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (1,2,4,8,12,24 hours), Day 3 (1,2,4,8,12,24 hours) and Day 4 post-dose at Day 5 (30 and 36 hours), Day 6 (48,54 and 60 hours), Day 7 (72,78 and 84 hours) and Day 8 (96 hours). The actual date and time of each blood sample collection was recorded.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=8 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 1, Pre-dose	0.00000 nanograms/milliliter Standard Deviation 0.00000	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 1, 1 hour	0.00000 nanograms/milliliter Standard Deviation 0.00000	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 1, 2 hours	0.02780 nanograms/milliliter Standard Deviation 0.02780	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 1, 4 hours	0.19470 nanograms/milliliter Standard Deviation 0.19470	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 1, 8 hours	0.31849 nanograms/milliliter Standard Deviation 0.31849	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 1, 12 hours	0.49735 nanograms/milliliter Standard Deviation 0.49735	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 1, 24 hours	0.86538 nanograms/milliliter Standard Deviation 0.86538	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 2, 1 hour	0.82164 nanograms/milliliter Standard Deviation 0.82164	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 2, 2 hours	0.91896 nanograms/milliliter Standard Deviation 0.91896	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 2, 4 hours	1.10081 nanograms/milliliter Standard Deviation 1.10081	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 2, 8 hours	1.18935 nanograms/milliliter Standard Deviation 1.18935	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 2, 12 hours	1.44756 nanograms/milliliter Standard Deviation 1.44756	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 2, 24 hours	2.11824 nanograms/milliliter Standard Deviation 2.11824	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 3, 1 hour	2.15994 nanograms/milliliter Standard Deviation 2.15994	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 3, 2 hours	2.17775 nanograms/milliliter Standard Deviation 2.17775	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 3, 4 hours	2.39909 nanograms/milliliter Standard Deviation 2.39909	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 3, 8 hours	2.30511 nanograms/milliliter Standard Deviation 2.30511	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 3, 12 hours	2.72968 nanograms/milliliter Standard Deviation 2.72968	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 3, 24 hours	3.40905 nanograms/milliliter Standard Deviation 3.40905	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 4, 1 hour	3.64494 nanograms/milliliter Standard Deviation 3.64494	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 4, 2 hours	3.76981 nanograms/milliliter Standard Deviation 3.76981	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 4, 4 hours	3.99425 nanograms/milliliter Standard Deviation 3.99425	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 4, 8 hours	3.88128 nanograms/milliliter Standard Deviation 3.88128	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 4, 12 hours	4.13984 nanograms/milliliter Standard Deviation 4.13984	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 4, 24 hours	5.35715 nanograms/milliliter Standard Deviation 5.35715	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 5, 30 hours	4.98988 nanograms/milliliter Standard Deviation 1.807766	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 5, 36 hours	4.63755 nanograms/milliliter Standard Deviation 1.629070	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 6, 48 hours	4.92234 nanograms/milliliter Standard Deviation 1.690833	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 6, 54 hours	4.44403 nanograms/milliliter Standard Deviation 1.834524	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 6, 60 hours	4.04828 nanograms/milliliter Standard Deviation 1.646939	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 7, 72 hours	4.02665 nanograms/milliliter Standard Deviation 1.592538	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 7, 78 hours	3.76244 nanograms/milliliter Standard Deviation 1.751219	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 7, 84 hours	3.45551 nanograms/milliliter Standard Deviation 1.522890	—	—	—
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A Day 8, 96 hours	3.30003 nanograms/milliliter Standard Deviation 1.364104	—	—	—

SECONDARY outcome

Timeframe: Day 1 (Pre-dose,1,4,8,12,24 hours), Day 2 (1,4,8,12,24 hours), Day 3 (1,4,8,12,24 hours), Day 6, Day 9, Day 12, Day 15 and follow-up (Day 17 to 19)

Population: PK Population

Blood samples were collected to assess the plasma concentration of GSK2646264 for Part B on Day 1 (Pre-dose,1,4,8,12,24 hours), Day 2 (1,4,8,12,24 hours), Day 3 (1,4,8,12,24 hours), Day 6, Day 9, Day 12, Day 15 and follow-up (Day 17 to 19). The actual date and time of each blood sample collection was recorded.

Outcome measures

SECONDARY outcome

Timeframe: Day 1 (Pre-dose,1 and 4 hours), Day 4 (Pre-dose and 4 hours), Day 7 (Pre-dose and 4 hours), Day 10, Day 15 and follow-up (Day 23)

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

Blood samples were collected to assess the plasma concentration of GSK2646264 for Part C on Day 1 (Pre-dose,1 and 4 hours), Day 4 (Pre-dose and 4 hours), Day 7 (Pre-dose and 4 hours), Day 10, Day 15 and follow-up. The actual date and time of each blood sample collection was recorded.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=4 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Plasma GSK2646264 PK Concentrations for Part C Day 1, Pre-dose, n=3	0.00000 nanograms/milliliter Standard Deviation 0.00000	—	—	—
Plasma GSK2646264 PK Concentrations for Part C Day 1, 4 hours, n=4	0.18048 nanograms/milliliter Standard Deviation 0.123670	—	—	—
Plasma GSK2646264 PK Concentrations for Part C Day 4, Pre-dose, n=3	1.22397 nanograms/milliliter Standard Deviation 0.963854	—	—	—
Plasma GSK2646264 PK Concentrations for Part C Day 4, 4 hours, n=3	1.37440 nanograms/milliliter Standard Deviation 0.961820	—	—	—
Plasma GSK2646264 PK Concentrations for Part C Day 7, Pre-dose, n=4	2.33635 nanograms/milliliter Standard Deviation 2.342202	—	—	—
Plasma GSK2646264 PK Concentrations for Part C Day 7, 4 hours, n=4	2.77940 nanograms/milliliter Standard Deviation 2.275138	—	—	—
Plasma GSK2646264 PK Concentrations for Part C Day 10,n=4	2.13075 nanograms/milliliter Standard Deviation 1.830816	—	—	—
Plasma GSK2646264 PK Concentrations for Part C Day 15,n=4	0.91718 nanograms/milliliter Standard Deviation 0.895466	—	—	—
Plasma GSK2646264 PK Concentrations for Part C Follow-up, n=4	0.44233 nanograms/milliliter Standard Deviation 0.349810	—	—	—

SECONDARY outcome

Timeframe: Pre dose, 1 ,2, 4, 8, 12 and 24 hours post-dose on Days 1,2 and Day 3

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

Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the AUC (0-T) was determined using the currently approved and validated software.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=9 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Area Under the Concentration-time Curve From Time 0 to t (AUC [0-t]) of GSK2646264 for Part A Day 1, n=3	0.5411 Hours*nanograms/milliliter Geometric Coefficient of Variation 45	—	—	—
Area Under the Concentration-time Curve From Time 0 to t (AUC [0-t]) of GSK2646264 for Part A Day 2,n=9	3.1462 Hours*nanograms/milliliter Geometric Coefficient of Variation 60	—	—	—
Area Under the Concentration-time Curve From Time 0 to t (AUC [0-t]) of GSK2646264 for Part A Day 3, n=9	15.2614 Hours*nanograms/milliliter Geometric Coefficient of Variation 66	—	—	—

SECONDARY outcome

Timeframe: Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (Pre-dose,1,2,4,8,12,24 hours), Day 3 (Pre-dose,1,2,4,8,12,24 hours) and Day 4 post-dose

Population: PK Population

Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the AUC (0-T) was determined using the currently approved and validated software.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=8 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
AUC (0-t) of GSK2646264 for Part A Day 3	60.2293 Hours*nanograms/milliliter Geometric Coefficient of Variation 40	—	—	—
AUC (0-t) of GSK2646264 for Part A Day 4	382.4520 Hours*nanograms/milliliter Geometric Coefficient of Variation 40	—	—	—
AUC (0-t) of GSK2646264 for Part A Day 1	8.6870 Hours*nanograms/milliliter Geometric Coefficient of Variation 86	—	—	—
AUC (0-t) of GSK2646264 for Part A Day 2	31.0600 Hours*nanograms/milliliter Geometric Coefficient of Variation 53	—	—	—

SECONDARY outcome

Timeframe: Pre dose, 1 ,2, 4, 8, 12 and 24 hours post-dose on Days 1,2 and Day 3

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

Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the Cmax was determined using the currently approved and validated software.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=9 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Maximum Plasma Concentration (Cmax) of GSK2646264 for Part A Day 1, n=3	0.07360 Nanograms/milliliter Geometric Coefficient of Variation 34	—	—	—
Maximum Plasma Concentration (Cmax) of GSK2646264 for Part A Day 2, n=9	0.25084 Nanograms/milliliter Geometric Coefficient of Variation 69	—	—	—
Maximum Plasma Concentration (Cmax) of GSK2646264 for Part A Day 3,n=9	0.90382 Nanograms/milliliter Geometric Coefficient of Variation 69	—	—	—

SECONDARY outcome

Timeframe: Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (Pre-dose,1,2,4,8,12,24 hours), Day 3 (Pre-dose,1,2,4,8,12,24 hours) and Day 4 post-dose

Population: PK Population

Blood samples were collected at the indicated time points to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the Cmax was determined using the currently approved and validated software.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=8 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Cmax of GSK2646264 for Part A Day 1	0.72391 Nanograms/milliliter Geometric Coefficient of Variation 72	—	—	—
Cmax of GSK2646264 for Part A Day 2	1.96715 Nanograms/milliliter Geometric Coefficient of Variation 43	—	—	—
Cmax of GSK2646264 for Part A Day 3	3.28320 Nanograms/milliliter Geometric Coefficient of Variation 34	—	—	—
Cmax of GSK2646264 for Part A Day 4	5.22144 Nanograms/milliliter Geometric Coefficient of Variation 41	—	—	—

SECONDARY outcome

Timeframe: Pre dose, 1 ,2, 4, 8, 12 and 24 hours post-dose on Days 1,2,3 and 4

Population: PK Population.

Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the AUC (0-24) was determined using the currently approved and validated software. NA indicated data was not collected due to insufficient participants with data.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=9 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC [0-24]) of GSK2646264 for Part A	NA Hours*nanograms/milliliter Geometric Coefficient of Variation NA NA indicated data was not collected due to insufficient participants with data.	—	—	—

SECONDARY outcome

Timeframe: Pre dose, 1 ,2, 4, 8, 12 and 24 hours post-dose on Days 1,2,3 and 4

Population: PK Population

Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the AUC (0-24) was determined using the currently approved and validated software.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=8 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC [0-24]) of GSK2646264 for Part A	97.8835 Hours*nanograms/milliliter Geometric Coefficient of Variation 37	—	—	—

SECONDARY outcome

Timeframe: Pre dose, 1 ,2, 4, 8, 12 and 24 hours post-dose on Days 1,2 and Day 3

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

Blood samples were collected at the indicated time points to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the tmax was determined using the currently approved and validated software.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=9 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Time to Cmax (Tmax) of GSK2646264 for Part A Day 1, n=3	19.60 hours Standard Deviation 6.585	—	—	—
Time to Cmax (Tmax) of GSK2646264 for Part A Day 2, n=9	21.52 hours Standard Deviation 5.074	—	—	—
Time to Cmax (Tmax) of GSK2646264 for Part A Day 3,n=9	20.32 hours Standard Deviation 7.267	—	—	—

SECONDARY outcome

Timeframe: Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (Pre-dose,1,2,4,8,12,24 hours), Day 3 (Pre-dose,1,2,4,8,12,24 hours) and Day 4 post-dose

Population: PK Population

Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the tmax was determined using the currently approved and validated software.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=8 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Tmax of GSK2646264 for Part A Day 1	23.85 hours Standard Deviation 0.053	—	—	—
Tmax of GSK2646264 for Part A Day 2	23.83 hours Standard Deviation 0.046	—	—	—
Tmax of GSK2646264 for Part A Day 3	22.29 hours Standard Deviation 4.158	—	—	—
Tmax of GSK2646264 for Part A Day 4	28.99 hours Standard Deviation 14.180	—	—	—

SECONDARY outcome

Timeframe: Pre dose, 1 ,2, 4, 8, 12 and 24 hours post-dose on Days 1,2,3 and 4

Population: PK Population

Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the t1/2 was determined using the currently approved and validated software. NA indicated t1/2 could not be calculated as we need at least 3 time points after Cmax within the same participant and this criteria could not be fulfilled due to lack of available data.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=9 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Terminal Half-life (t1/2) of GSK2646264 for Part A	NA hours Standard Deviation NA NA indicated t1/2 could not be calculated as we need at least 3 time points after Cmax within the same participant and this criteria could not be fulfilled due to lack of available data.	—	—	—

SECONDARY outcome

Timeframe: Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (Pre-dose,1,2,4,8,12,24 hours), Day 3 (Pre-dose,1,2,4,8,12,24 hours) and Day 4 post-dose at Day 5 (30 and 36 hours), Day 6 (48,54 and 60 hours), Day 7 (72,78 and 84 hours) and Day 8 (96 hours)

Population: PK Population

Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the t1/2 was determined using the currently approved and validated software. NA indicated t1/2 could not be calculated as we need at least 3 time points after Cmax within the same participant and this criteria could not be fulfilled due to lack of available data.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=8 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
t1/2 of GSK2646264 for Part A	NA hours Standard Deviation NA NA indicated t1/2 could not be calculated as we need at least 3 time points after Cmax within the same participant and this criteria could not be fulfilled due to lack of available data.	—	—	—

SECONDARY outcome

Timeframe: Pre dose, 1 ,2, 4, 8, 12 hours post-dose on Days 1,2,3 and 24 hours post last dose on Day 3

Population: PK Population

Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the AUC (0-t) was determined using the currently approved and validated software.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=3 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% n=6 Participants CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
AUC [0-t] of GSK2646264 for Part B Day 1	40.5235 Hours*nanograms/milliliter Geometric Coefficient of Variation 92	18.7840 Hours*nanograms/milliliter Geometric Coefficient of Variation 101	—	—
AUC [0-t] of GSK2646264 for Part B Day 2	100.6152 Hours*nanograms/milliliter Geometric Coefficient of Variation 18	46.5654 Hours*nanograms/milliliter Geometric Coefficient of Variation 96	—	—
AUC [0-t] of GSK2646264 for Part B Day 3	825.1809 Hours*nanograms/milliliter Geometric Coefficient of Variation 22	379.8602 Hours*nanograms/milliliter Geometric Coefficient of Variation 109	—	—

SECONDARY outcome

Timeframe: Pre dose, 1 ,2, 4, 8, 12 hours post-dose on Days 1,2,3 and 24 hours post last dose on Day 3 (Day 4)

Population: PK Population.

Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the Cmax was determined using the currently approved and validated software.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=3 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% n=6 Participants CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Cmax of GSK2646264 for Part B Day 1	2.71563 Nanograms/milliliter Geometric Coefficient of Variation 69	1.30673 Nanograms/milliliter Geometric Coefficient of Variation 109	—	—
Cmax of GSK2646264 for Part B Day 2	5.14144 Nanograms/milliliter Geometric Coefficient of Variation 6	2.41207 Nanograms/milliliter Geometric Coefficient of Variation 92	—	—
Cmax of GSK2646264 for Part B Day 3	7.51684 Nanograms/milliliter Geometric Coefficient of Variation 8	2.89771 Nanograms/milliliter Geometric Coefficient of Variation 120	—	—

SECONDARY outcome

Timeframe: Pre dose, 1 ,2, 4, 8, 12 hours post-dose on Days 1,2,3 and 24 hours post last dose on Day 3 (Day 4)

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

Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the AUC (0-24) was determined using the currently approved and validated software. NA indicates that geometric coefficient of variation could not be computed for Part B (3.5% BSA) GSK2646264 1% as a single participant was analyzed on Day 2.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=3 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% n=6 Participants CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
AUC (0-24) of GSK2646264 for Part B Day 2, n=0, 1	—	34.4377 Hours*nanograms/milliliter Geometric Coefficient of Variation NA NA indicates that geometric coefficient of variation could not be computed for Part B (3.5% BSA) GSK2646264 1% as a single participant was analyzed on Day 2.	—	—
AUC (0-24) of GSK2646264 for Part B Day 3, n=3, 6	166.6914 Hours*nanograms/milliliter Geometric Coefficient of Variation 14	68.2224 Hours*nanograms/milliliter Geometric Coefficient of Variation 120	—	—

SECONDARY outcome

Timeframe: Pre dose, 1 ,2, 4, 8, 12 hours post-dose on Days 1,2,3 and 24 hours post last dose on Day 3

Population: PK Population. Only those participants available at the indicated time points were analyzed.

Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the AUC (0-infinity) was determined using the currently approved and validated software.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=3 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% n=6 Participants CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Area Under the Concentration-time Curve From Time 0 to Infinity (AUC [0-inf]) of GSK2646264 for Part B Day 3	844.3091 Hours*nanograms/milliliter Geometric Coefficient of Variation 22	390.7973 Hours*nanograms/milliliter Geometric Coefficient of Variation 109	—	—

SECONDARY outcome

Timeframe: Pre dose, 1 ,2, 4, 8, 12 hours post-dose on Days 1,2,3 and 24 hours post last dose on Day 3

Population: PK Population

Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the t1/2 was determined using the currently approved and validated software.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=3 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% n=6 Participants CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Terminal Half-life (t1/2) of GSK2646264 for Part B Day 3	59.69 hours Geometric Coefficient of Variation 4.433	64.01 hours Geometric Coefficient of Variation 11.220	—	—

SECONDARY outcome

Timeframe: Pre dose, 1 ,2, 4, 8, 12 hours post-dose on Days 1,2,3 and 24 hours post last dose on Day 3

Population: PK Population

Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the tmax was determined using the currently approved and validated software.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=3 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% n=6 Participants CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Tmax of GSK2646264 for Part B Day 1	19.67 hours Standard Deviation 23.6	17.85 hours Standard Deviation 6.373	—	—
Tmax of GSK2646264 for Part B Day 2	16.93 hours Standard Deviation 23.5	21.13 hours Standard Deviation 6.436	—	—
Tmax of GSK2646264 for Part B Day 3	13.33 hours Standard Deviation 24.0	12.62 hours Standard Deviation 6.378	—	—

SECONDARY outcome

Timeframe: Pre dose and 4 hours post-dose on Days 1, 4 and 7

Population: PK Population.

Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the Cmax was determined using the currently approved and validated software.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=4 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Cmax of GSK2646264 for Part C	1.85336 Nanograms/milliliter Geometric Coefficient of Variation 185	—	—	—

SECONDARY outcome

Timeframe: Pre dose and 4 hours post-dose on Days 1, 4 and 7

Population: PK Population

Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the tmax was determined using the currently approved and validated software.

Outcome measures

Outcome measures
Measure	Part A-GSK2646264 0.5% n=4 Participants Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3.	Part B (10% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 10% BSA (5% BSA on each arm) on Days 1, 2 and 3.	Part B (3.5% BSA)-Placebo CU participants received matching placebo treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.	Part B (3.5% BSA) GSK2646264 1% CU participants received 1% strength GSK2646264 treatment to an area of 3.5% BSA (spread over the 2 arms) on Days 1, 2 and 3.
Tmax of GSK2646264 for Part C	4.10 hours Standard Deviation 0.082	—	—	—

SECONDARY outcome

Timeframe: Pre dose and 4 hours post-dose on Days 1, 4 and 7

Population: PK Population

Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the t1/2 was determined using the currently approved and validated software. NA indicated data was not collected due to insufficient number of participants with data to calculate half life.