Trial Outcomes & Findings for 3 Month PHI PAD PoM Study (NCT NCT02135848)

NCT ID: NCT02135848

Last Updated: 2017-10-20

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 AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. 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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 46 participants
• Primary outcome timeframe: Up to 67 days
• Results posted on: 2017-10-20

Participant Flow

This study was conducted at 12 centers in the United States from 15-October-2010 to 01-November-2011.

Participant milestones

Measure	GSK1278863 Eligible participants received an initial single high dose of 300 milligram (mg) GSK1278863 tablets orally followed by a 14-day washout period. After completing the washout period, participants received repeated dose of 15 mg GSK1278863 tablets orally once daily for 14 days.	Placebo Eligible participants received single dose of placebo matched with 300 mg GSK1278863 tablets orally followed by a 14-day washout period. After completing the washout period, participants received placebo matched with 15 mg GSK1278863 tablets orally once daily for 14 days.
Overall Study STARTED	26	20
Overall Study COMPLETED	23	19
Overall Study NOT COMPLETED	3	1

Reasons for withdrawal

Measure	GSK1278863 Eligible participants received an initial single high dose of 300 milligram (mg) GSK1278863 tablets orally followed by a 14-day washout period. After completing the washout period, participants received repeated dose of 15 mg GSK1278863 tablets orally once daily for 14 days.	Placebo Eligible participants received single dose of placebo matched with 300 mg GSK1278863 tablets orally followed by a 14-day washout period. After completing the washout period, participants received placebo matched with 15 mg GSK1278863 tablets orally once daily for 14 days.
Overall Study Adverse Event	2	0
Overall Study Withdrawal by Subject	1	1

Baseline Characteristics

3 Month PHI PAD PoM Study

Baseline characteristics by cohort

Measure	GSK1278863 n=26 Participants Eligible participants received an initial single high dose of 300 mg GSK1278863 tablets orally followed by a 14-day washout period. After completing the washout period, participants received repeated dose of 15 mg GSK1278863 tablets orally once daily for 14 days.	Placebo n=20 Participants Eligible participants received single dose of placebo matched with 300 mg GSK1278863 tablets orally followed by a 14-day washout period. After completing the washout period, participants received placebo matched with 15 mg GSK1278863 tablets orally once daily for 14 days.	Total n=46 Participants Total of all reporting groups
Age, Continuous	68.4 Years STANDARD_DEVIATION 9.50 • n=5 Participants	69.4 Years STANDARD_DEVIATION 7.65 • n=7 Participants	68.8 Years STANDARD_DEVIATION 8.66 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	14 Participants n=7 Participants	33 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) White	19 Participants n=5 Participants	14 Participants n=7 Participants	33 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 67 days

Population: Safety population which comprised of all participants who received at least one dose of study medication.

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 AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. 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

Measure	GSK1278863 300 mg n=26 Participants Eligible participants received an initial single high dose of 300 mg GSK1278863 tablets orally.	Placebo Matched With GSK1278863 300 mg n=20 Participants Eligible participants received single dose of placebo matched with 300 mg GSK1278863 tablets orally.	GSK1278863 15 mg n=23 Participants Eligible participants received repeated dose of 15 mg GSK1278863 tablets orally once daily for 14 days.	Placebo Matched With GSK1278863 15 mg n=19 Participants Eligible participants received placebo matched with 15 mg GSK1278863 tablets orally once daily for 14 days.
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) AE	14 Participants	6 Participants	9 Participants	3 Participants
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) SAE	2 Participants	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to 39 days

Population: Safety Population. Only those participants with data available at the indicated time points were analyzed.

Twelve lead ECGs were recorded with the participant lying supine, having rested in this position for at least 5 minutes before each recording. Full 12 lead ECGs were recorded using an ECG device that automatically calculated the heart rate and measured PR, QRS, RR, QT and QT, QT corrected by Bazett's formula (QTcB) and QT corrected by Fridericia's formula (QTcF) intervals. Number of participants with abnormal (not clinically significant [NCS] and clinically significant [CS]) ECG findings are presented.

Outcome measures

Measure	GSK1278863 300 mg n=26 Participants Eligible participants received an initial single high dose of 300 mg GSK1278863 tablets orally.	Placebo Matched With GSK1278863 300 mg n=20 Participants Eligible participants received single dose of placebo matched with 300 mg GSK1278863 tablets orally.	GSK1278863 15 mg n=23 Participants Eligible participants received repeated dose of 15 mg GSK1278863 tablets orally once daily for 14 days.	Placebo Matched With GSK1278863 15 mg n=19 Participants Eligible participants received placebo matched with 15 mg GSK1278863 tablets orally once daily for 14 days.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Acute Day 1, 2.5 hour; Abnormal CS	0 Participants	0 Participants	—	—
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Acute Day 1, Pre-dose; Abnormal NCS	14 Participants	16 Participants	—	—
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Acute Day 1, Pre-dose; Abnormal CS	0 Participants	0 Participants	—	—
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Acute Day 1, 2.5 hour; Abnormal NCS	15 Participants	14 Participants	—	—
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Chronic Day 1, Pre-dose; Abnormal NCS	—	—	12 Participants	14 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Chronic Day 1, Pre-dose; Abnormal CS	—	—	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Chronic Day 1, 2.5 hour; Abnormal NCS	—	—	8 Participants	14 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Chronic Day 1, 2.5 hour; Abnormal CS	—	—	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings End of treatment, Pre-dose; Abnormal NCS	—	—	15 Participants	14 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings End of treatment, Pre-dose; Abnormal CS	—	—	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Early termination, Pre-dose; Abnormal NCS	2 Participants	—	—	—
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Early termination, Pre-dose; Abnormal CS	1 Participants	—	—	—

PRIMARY outcome

Timeframe: Up to 39 days

Population: Safety Population.

Vital signs included heart rate, systolic and diastolic blood pressure and were performed with the participant in a supine position after the participant had rested for at least 5 minutes. Number of participants with vital signs of potential clinical importance are presented.

Outcome measures

Measure	GSK1278863 300 mg n=26 Participants Eligible participants received an initial single high dose of 300 mg GSK1278863 tablets orally.	Placebo Matched With GSK1278863 300 mg n=20 Participants Eligible participants received single dose of placebo matched with 300 mg GSK1278863 tablets orally.	GSK1278863 15 mg n=23 Participants Eligible participants received repeated dose of 15 mg GSK1278863 tablets orally once daily for 14 days.	Placebo Matched With GSK1278863 15 mg n=19 Participants Eligible participants received placebo matched with 15 mg GSK1278863 tablets orally once daily for 14 days.
Number of Participants With Vital Signs of Potential Clinical Importance	3 Participants	1 Participants	2 Participants	3 Participants

PRIMARY outcome

Timeframe: Up to 67 days

Population: Safety Population.

Clinical chemistry analyte of potential clinical concern included albumin, calcium, creatinine, glucose, magnesium, phosphorus, potassium, sodium and bicarbonate. Number of participants with clinical chemistry abnormalities of potential clinical importance are presented.

Outcome measures

Measure	GSK1278863 300 mg n=26 Participants Eligible participants received an initial single high dose of 300 mg GSK1278863 tablets orally.	Placebo Matched With GSK1278863 300 mg n=20 Participants Eligible participants received single dose of placebo matched with 300 mg GSK1278863 tablets orally.	GSK1278863 15 mg n=23 Participants Eligible participants received repeated dose of 15 mg GSK1278863 tablets orally once daily for 14 days.	Placebo Matched With GSK1278863 15 mg n=19 Participants Eligible participants received placebo matched with 15 mg GSK1278863 tablets orally once daily for 14 days.
Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance High Creatinine	1 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance High Glucose	5 Participants	2 Participants	5 Participants	3 Participants
Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance High Calcium	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance High Potassium	1 Participants	1 Participants	2 Participants	1 Participants
Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance Low Carbon-dioxide content	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance High Carbon-dioxide content	0 Participants	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to 67 days

Population: Safety Population.

Hematology parameters included platelet count, red blood cell (RBC) count, white blood cell WBC count (absolute), hemoglobin, hematocrit, Mean corpuscular volume (MCV), Mean corpuscular hemoglobin (MCH), Mean corpuscular hemoglobin concentration (MCHC), neutrophils, lymphocytes, monocytes, eosinophils and basophils. Number of participants with clinical hematology abnormalities of potential clinical importance are presented.

Outcome measures

Measure	GSK1278863 300 mg n=26 Participants Eligible participants received an initial single high dose of 300 mg GSK1278863 tablets orally.	Placebo Matched With GSK1278863 300 mg n=20 Participants Eligible participants received single dose of placebo matched with 300 mg GSK1278863 tablets orally.	GSK1278863 15 mg Eligible participants received repeated dose of 15 mg GSK1278863 tablets orally once daily for 14 days.	Placebo Matched With GSK1278863 15 mg Eligible participants received placebo matched with 15 mg GSK1278863 tablets orally once daily for 14 days.
Number of Participants With Clinical Hematology Abnormalities of Potential Clinical Importance	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 39

Population: Pharmacodynamic population comprised of all participants who provided pharmacodynamic data, i.e. bilateral heel-raise data or six-minute-walk-test data. Only those participants with data available at the indicated time points were analyzed.

At Visit 1 (-21 to -10 days), the participant was introduced to the bilateral heel raise test (BHRT). Test familiarization consisted of the participant performing heel raises to the onset of claudication. The BHRT was conducted with an electrogoniometer instrumented on the index leg. Successive heel raise repetitions were performed once every other second until the participant stopped due to intolerable claudication pain or fatigue, or other criteria for stopping the test were met. The index leg was defined as the leg that met the inclusion symptomatic and hemodynamic criteria (ankle brachial index [ABI] ≤ 0.90) with the lowest ABI considered if both legs were affected. Baseline was Day 1. Change from Baseline was post-Baseline values minus Baseline values.

Outcome measures

Measure	GSK1278863 300 mg n=26 Participants Eligible participants received an initial single high dose of 300 mg GSK1278863 tablets orally.	Placebo Matched With GSK1278863 300 mg n=20 Participants Eligible participants received single dose of placebo matched with 300 mg GSK1278863 tablets orally.	GSK1278863 15 mg Eligible participants received repeated dose of 15 mg GSK1278863 tablets orally once daily for 14 days.	Placebo Matched With GSK1278863 15 mg Eligible participants received placebo matched with 15 mg GSK1278863 tablets orally once daily for 14 days.
Change From Baseline in Total Number of Contractions to Onset of Claudication Chronic Day 1, 3 hour	3.00 Contractions Standard Deviation 9.4	0.83 Contractions Standard Deviation 8.6	—	—
Change From Baseline in Total Number of Contractions to Onset of Claudication Acute Day 1, 3 hour	2.52 Contractions Standard Deviation 7.7	-1.67 Contractions Standard Deviation 6.5	—	—
Change From Baseline in Total Number of Contractions to Onset of Claudication Acute Day 2, Pre-dose	3.77 Contractions Standard Deviation 8.6	-0.94 Contractions Standard Deviation 4.8	—	—
Change From Baseline in Total Number of Contractions to Onset of Claudication Chronic Day 1, Pre-dose	5.68 Contractions Standard Deviation 10.0	-1.56 Contractions Standard Deviation 5.1	—	—
Change From Baseline in Total Number of Contractions to Onset of Claudication End of treatment, Pre-dose	2.90 Contractions Standard Deviation 9.2	-0.83 Contractions Standard Deviation 6.4	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 39

Population: Pharmacodynamic population. Only those participants available at the specified time points were analyzed.

BHRT is a method to assess muscle performance in participants with claudication. Participants with peripheral artery disease (PAD) and claudication experience reproducible symptoms of leg pain during walking exercise. The symptom of claudication is due to exercise-induced ischemia of muscles in legs, most commonly in calf muscles. At Visit 1 (-21 to -10 days), the participant was introduced to BHRT. Test familiarization consisted of the participant performing heel raises to onset of claudication. BHRT was conducted with an electrogoniometer instrumented on the index leg (leg that met the inclusion symptomatic and hemodynamic criteria [ABI ≤ 0.90] with the lowest ABI considered if both legs were affected). Successive heel raise repetitions were performed once every other second until participant stopped due to intolerable claudication pain/fatigue, or other criteria for stopping the test were met. Baseline was Day 1. Change from Baseline was post-Baseline values minus Baseline values.

Outcome measures

Measure	GSK1278863 300 mg n=26 Participants Eligible participants received an initial single high dose of 300 mg GSK1278863 tablets orally.	Placebo Matched With GSK1278863 300 mg n=20 Participants Eligible participants received single dose of placebo matched with 300 mg GSK1278863 tablets orally.	GSK1278863 15 mg Eligible participants received repeated dose of 15 mg GSK1278863 tablets orally once daily for 14 days.	Placebo Matched With GSK1278863 15 mg Eligible participants received placebo matched with 15 mg GSK1278863 tablets orally once daily for 14 days.
Change From Baseline in Total Work Performed to Onset of Claudication Chronic Day 1, Pre-dose	24.17 kilogram-meters Standard Deviation 38.7	-15.69 kilogram-meters Standard Deviation 45.0	—	—
Change From Baseline in Total Work Performed to Onset of Claudication Acute Day 1, 3 hour	14.66 kilogram-meters Standard Deviation 42.0	-8.12 kilogram-meters Standard Deviation 52.5	—	—
Change From Baseline in Total Work Performed to Onset of Claudication Acute Day 2, Pre-dose	12.46 kilogram-meters Standard Deviation 42.5	-14.61 kilogram-meters Standard Deviation 55.2	—	—
Change From Baseline in Total Work Performed to Onset of Claudication Chronic Day 1, 3 hour	11.23 kilogram-meters Standard Deviation 40.6	-3.03 kilogram-meters Standard Deviation 68.0	—	—
Change From Baseline in Total Work Performed to Onset of Claudication End of treatment, Pre-dose	8.13 kilogram-meters Standard Deviation 42.1	-15.60 kilogram-meters Standard Deviation 59.1	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 39

Population: Pharmacodynamic population. Only those participants available at the specified time points were analyzed.

BHRT is a method to assess muscle performance in participants with claudication. Participants with PAD and claudication experience reproducible symptoms of leg pain during walking exercise. The symptom of claudication is due to exercise-induced ischemia of muscles in legs, most commonly in calf muscles. At Visit 1 (-21 to -10 days), the participant was introduced to the BHRT. Test familiarization consisted of the participant performing heel raises to the onset of claudication. The BHRT was conducted with an electrogoniometer instrumented on the index leg (the leg that met the inclusion symptomatic and hemodynamic criteria [ABI ≤ 0.90] with the lowest ABI considered if both legs were affected). Successive heel raise repetitions were performed once every other second until the participant stopped due to intolerable claudication pain or fatigue, or other criteria for stopping the test were met. Baseline was Day 1. Change from Baseline was post-Baseline values minus Baseline values.

Outcome measures

Measure	GSK1278863 300 mg n=26 Participants Eligible participants received an initial single high dose of 300 mg GSK1278863 tablets orally.	Placebo Matched With GSK1278863 300 mg n=20 Participants Eligible participants received single dose of placebo matched with 300 mg GSK1278863 tablets orally.	GSK1278863 15 mg Eligible participants received repeated dose of 15 mg GSK1278863 tablets orally once daily for 14 days.	Placebo Matched With GSK1278863 15 mg Eligible participants received placebo matched with 15 mg GSK1278863 tablets orally once daily for 14 days.
Change From Baseline in Total Exercise Time to Onset of Claudication Acute Day 1, 3 hour	4.39 Seconds Standard Deviation 15.7	-3.34 Seconds Standard Deviation 13.4	—	—
Change From Baseline in Total Exercise Time to Onset of Claudication Acute Day 2, Pre-dose	8.00 Seconds Standard Deviation 17.2	-3.96 Seconds Standard Deviation 14.4	—	—
Change From Baseline in Total Exercise Time to Onset of Claudication Chronic Day 1, Pre-dose	10.50 Seconds Standard Deviation 19.9	-3.71 Seconds Standard Deviation 11.1	—	—
Change From Baseline in Total Exercise Time to Onset of Claudication Chronic Day 1, 3 hour	5.63 Seconds Standard Deviation 18.5	1.25 Seconds Standard Deviation 18.3	—	—
Change From Baseline in Total Exercise Time to Onset of Claudication End of treatment, Pre-dose	5.03 Seconds Standard Deviation 18.7	-1.05 Seconds Standard Deviation 11.8	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 39

Population: Pharmacodynamic population. Only those participants available at the specified time points were analyzed.

BHRT is a method to assess muscle performance in participants with claudication. Participants with PAD and claudication experience reproducible symptoms of leg pain during walking exercise. The symptom of claudication is due to exercise-induced ischemia of muscles in legs, most commonly in calf muscles. At Visit 1 (-21 to -10 days), the participant was introduced to the BHRT. Test familiarization consisted of the participant performing heel raises to the onset of claudication. The BHRT was conducted with an electrogoniometer instrumented on the index leg (the leg that met the inclusion symptomatic and hemodynamic criteria [ABI ≤ 0.90] with the lowest ABI considered if both legs were affected). Successive heel raise repetitions were performed once every other second until the participant stopped due to intolerable claudication pain or fatigue, or other criteria for stopping the test were met. Baseline was Day 1. Change from Baseline was post-Baseline values minus Baseline values.

Outcome measures

Measure	GSK1278863 300 mg n=26 Participants Eligible participants received an initial single high dose of 300 mg GSK1278863 tablets orally.	Placebo Matched With GSK1278863 300 mg n=20 Participants Eligible participants received single dose of placebo matched with 300 mg GSK1278863 tablets orally.	GSK1278863 15 mg Eligible participants received repeated dose of 15 mg GSK1278863 tablets orally once daily for 14 days.	Placebo Matched With GSK1278863 15 mg Eligible participants received placebo matched with 15 mg GSK1278863 tablets orally once daily for 14 days.
Change From Baseline in Total Number of Contractions to Claudication-limited Maximal Muscle Performance Acute Day 2, Pre-dose	1.48 Contractions Standard Deviation 10.1	-0.94 Contractions Standard Deviation 5.6	—	—
Change From Baseline in Total Number of Contractions to Claudication-limited Maximal Muscle Performance End of treatment, Pre-dose	3.45 Contractions Standard Deviation 10.1	-1.11 Contractions Standard Deviation 8.1	—	—
Change From Baseline in Total Number of Contractions to Claudication-limited Maximal Muscle Performance Acute Day 1, 3 hour	1.00 Contractions Standard Deviation 7.6	-2.17 Contractions Standard Deviation 6.4	—	—
Change From Baseline in Total Number of Contractions to Claudication-limited Maximal Muscle Performance Chronic Day 1, Pre-dose	4.55 Contractions Standard Deviation 8.3	-1.83 Contractions Standard Deviation 5.6	—	—
Change From Baseline in Total Number of Contractions to Claudication-limited Maximal Muscle Performance Chronic Day 1, 3 hour	3.45 Contractions Standard Deviation 10.0	-0.67 Contractions Standard Deviation 6.9	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 39

Population: Pharmacodynamic population. Only those participants available at the specified time points were analyzed.

BHRT is a method to assess muscle performance in participants with claudication. Participants with PAD and claudication experience reproducible symptoms of leg pain during walking exercise. The symptom of claudication is due to exercise-induced ischemia of muscles in legs, most commonly in calf muscles. At Visit 1 (-21 to -10 days), the participant was introduced to the BHRT. Test familiarization consisted of the participant performing heel raises to the onset of claudication. The BHRT was conducted with an electrogoniometer instrumented on the index leg (the leg that met the inclusion symptomatic and hemodynamic criteria [ABI ≤ 0.90] with the lowest ABI considered if both legs were affected). Successive heel raise repetitions were performed once every other second until the participant stopped due to intolerable claudication pain or fatigue, or other criteria for stopping the test were met. Baseline was Day 1. Change from Baseline was post-Baseline values minus Baseline values.

Outcome measures

Measure	GSK1278863 300 mg n=26 Participants Eligible participants received an initial single high dose of 300 mg GSK1278863 tablets orally.	Placebo Matched With GSK1278863 300 mg n=20 Participants Eligible participants received single dose of placebo matched with 300 mg GSK1278863 tablets orally.	GSK1278863 15 mg Eligible participants received repeated dose of 15 mg GSK1278863 tablets orally once daily for 14 days.	Placebo Matched With GSK1278863 15 mg Eligible participants received placebo matched with 15 mg GSK1278863 tablets orally once daily for 14 days.
Change From Baseline in Total Work Performed to Claudication-limited Maximal Muscle Performance Acute Day 2, Pre-dose	5.11 kilogram-meters Standard Deviation 55.4	-11.35 kilogram-meters Standard Deviation 62.2	—	—
Change From Baseline in Total Work Performed to Claudication-limited Maximal Muscle Performance Chronic Day 1, Pre-dose	22.20 kilogram-meters Standard Deviation 36.5	-10.84 kilogram-meters Standard Deviation 62.3	—	—
Change From Baseline in Total Work Performed to Claudication-limited Maximal Muscle Performance Chronic Day 1, 3 hour	14.40 kilogram-meters Standard Deviation 46.8	-4.04 kilogram-meters Standard Deviation 68.9	—	—
Change From Baseline in Total Work Performed to Claudication-limited Maximal Muscle Performance Acute Day 1, 3 hour	11.32 kilogram-meters Standard Deviation 46.1	-6.20 kilogram-meters Standard Deviation 53.4	—	—
Change From Baseline in Total Work Performed to Claudication-limited Maximal Muscle Performance End of treatment, Pre-dose	6.75 kilogram-meters Standard Deviation 37.1	-14.22 kilogram-meters Standard Deviation 75.6	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 39

Population: Pharmacodynamic population. Only those participants available at the specified time points were analyzed.

BHRT is a method to assess muscle performance in participants with claudication. Participants with PAD and claudication experience reproducible symptoms of leg pain during walking exercise. The symptom of claudication is due to exercise-induced ischemia of muscles in legs, most commonly in calf muscles. At Visit 1 (-21 to -10 days), the participant was introduced to the BHRT. Test familiarization consisted of the participant performing heel raises to the onset of claudication. The BHRT was conducted with an electrogoniometer instrumented on the index leg (the leg that met the inclusion symptomatic and hemodynamic criteria [ABI ≤ 0.90] with the lowest ABI considered if both legs were affected). Successive heel raise repetitions were performed once every other second until the participant stopped due to intolerable claudication pain or fatigue, or other criteria for stopping the test were met. Baseline was Day 1. Change from Baseline was post-Baseline values minus Baseline values.

Outcome measures

Measure	GSK1278863 300 mg n=26 Participants Eligible participants received an initial single high dose of 300 mg GSK1278863 tablets orally.	Placebo Matched With GSK1278863 300 mg n=20 Participants Eligible participants received single dose of placebo matched with 300 mg GSK1278863 tablets orally.	GSK1278863 15 mg Eligible participants received repeated dose of 15 mg GSK1278863 tablets orally once daily for 14 days.	Placebo Matched With GSK1278863 15 mg Eligible participants received placebo matched with 15 mg GSK1278863 tablets orally once daily for 14 days.
Change From Baseline in Total Exercise Time to Claudication-limited Maximal Muscle Performance Acute Day 1, 3 hour	0.15 seconds Standard Deviation 14.7	-5.41 seconds Standard Deviation 13.3	—	—
Change From Baseline in Total Exercise Time to Claudication-limited Maximal Muscle Performance Acute Day 2, Pre-dose	2.18 seconds Standard Deviation 21.1	-5.06 seconds Standard Deviation 15.8	—	—
Change From Baseline in Total Exercise Time to Claudication-limited Maximal Muscle Performance Chronic Day 1, Pre-dose	5.71 seconds Standard Deviation 15.7	-4.91 seconds Standard Deviation 12.3	—	—
Change From Baseline in Total Exercise Time to Claudication-limited Maximal Muscle Performance Chronic Day 1, 3 hour	4.89 seconds Standard Deviation 18.6	-2.92 seconds Standard Deviation 15.2	—	—
Change From Baseline in Total Exercise Time to Claudication-limited Maximal Muscle Performance End of treatment, Pre-dose	4.59 seconds Standard Deviation 21.1	-2.69 seconds Standard Deviation 15.7	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 39

Population: Pharmacodynamic Population. Only those participants available at the specified time points were analyzed.

The Six-Minute Walk Test was performed by the participant walking at a self-selected pace for 6 minutes through a pre-defined walking course. When the Six-Minute Walk Test and Bilateral Heel Raise Test were conducted at the same study visit, the participant was allowed to rest a minimum of one hour between these tests. Baseline was Day 1. Change from Baseline was post-Baseline values minus Baseline values.

Outcome measures

Measure	GSK1278863 300 mg n=26 Participants Eligible participants received an initial single high dose of 300 mg GSK1278863 tablets orally.	Placebo Matched With GSK1278863 300 mg n=20 Participants Eligible participants received single dose of placebo matched with 300 mg GSK1278863 tablets orally.	GSK1278863 15 mg Eligible participants received repeated dose of 15 mg GSK1278863 tablets orally once daily for 14 days.	Placebo Matched With GSK1278863 15 mg Eligible participants received placebo matched with 15 mg GSK1278863 tablets orally once daily for 14 days.
Change From Baseline in the Maximal Distance Covered During a Six-Minute Walk Test Acute Day 1, 2 hour	-52.88 Feet Standard Deviation 140.3	-11.60 Feet Standard Deviation 64.3	—	—
Change From Baseline in the Maximal Distance Covered During a Six-Minute Walk Test Acute Day 2, Pre-dose	-42.25 Feet Standard Deviation 160.9	-7.11 Feet Standard Deviation 116.2	—	—
Change From Baseline in the Maximal Distance Covered During a Six-Minute Walk Test Chronic Day 1, Pre-dose	8.43 Feet Standard Deviation 139.7	-31.89 Feet Standard Deviation 138.6	—	—
Change From Baseline in the Maximal Distance Covered During a Six-Minute Walk Test Chronic Day 1, 2 hour	-6.43 Feet Standard Deviation 145.2	-26.53 Feet Standard Deviation 166.6	—	—
Change From Baseline in the Maximal Distance Covered During a Six-Minute Walk Test End of treatment, Pre-dose	14.57 Feet Standard Deviation 163.9	-47.47 Feet Standard Deviation 192.8	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 39

Population: Pharmacodynamic Population. Only those participants available at the specified time points were analyzed.

Blood samples for analysis of fasting levels of erythropoietin, was collected up to end of treatment or early termination. Baseline acute was Day 1 and Baseline chronic was Day 21. Change from Baseline was post-Baseline values minus Baseline values.

Outcome measures

Measure	GSK1278863 300 mg n=26 Participants Eligible participants received an initial single high dose of 300 mg GSK1278863 tablets orally.	Placebo Matched With GSK1278863 300 mg n=20 Participants Eligible participants received single dose of placebo matched with 300 mg GSK1278863 tablets orally.	GSK1278863 15 mg Eligible participants received repeated dose of 15 mg GSK1278863 tablets orally once daily for 14 days.	Placebo Matched With GSK1278863 15 mg Eligible participants received placebo matched with 15 mg GSK1278863 tablets orally once daily for 14 days.
Change From Baseline in Erythropoietin Concentration Chronic Day 1, 3 hour	1.00 Units per Liter Standard Deviation 8.435	-4.81 Units per Liter Standard Deviation 8.067	—	—
Change From Baseline in Erythropoietin Concentration End of treatment, Pre-dose	0.78 Units per Liter Standard Deviation 11.360	-1.60 Units per Liter Standard Deviation 13.421	—	—
Change From Baseline in Erythropoietin Concentration Acute Day 1, 2.5 hour	8.10 Units per Liter Standard Deviation 14.119	-2.54 Units per Liter Standard Deviation 3.718	—	—
Change From Baseline in Erythropoietin Concentration Acute Day 1, 3 hour	53.98 Units per Liter Standard Deviation 87.176	-2.25 Units per Liter Standard Deviation 4.416	—	—
Change From Baseline in Erythropoietin Concentration Acute Day 2, Pre-dose	907.43 Units per Liter Standard Deviation 561.105	-0.79 Units per Liter Standard Deviation 6.889	—	—
Change From Baseline in Erythropoietin Concentration Chronic Day 1, Pre-dose	-1.05 Units per Liter Standard Deviation 8.228	-2.39 Units per Liter Standard Deviation 6.275	—	—
Change From Baseline in Erythropoietin Concentration Chronic Day 1, 2.5 hour	-2.24 Units per Liter Standard Deviation 7.349	-5.18 Units per Liter Standard Deviation 7.905	—	—
Change From Baseline in Erythropoietin Concentration Early termination	-10.15 Units per Liter Standard Deviation 7.283	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 39

Population: Pharmacodynamic population. Only those participants available at the specified time points were analyzed.

Blood samples for analysis of fasting levels of hemoglobin was collected up to end of treatment or early termination. Baseline acute was Day 1 and Baseline chronic was Day 21. Change from Baseline was post-Baseline values minus Baseline values.

Outcome measures

Measure	GSK1278863 300 mg n=26 Participants Eligible participants received an initial single high dose of 300 mg GSK1278863 tablets orally.	Placebo Matched With GSK1278863 300 mg n=20 Participants Eligible participants received single dose of placebo matched with 300 mg GSK1278863 tablets orally.	GSK1278863 15 mg Eligible participants received repeated dose of 15 mg GSK1278863 tablets orally once daily for 14 days.	Placebo Matched With GSK1278863 15 mg Eligible participants received placebo matched with 15 mg GSK1278863 tablets orally once daily for 14 days.
Change From Baseline in Hemoglobin Acute Day 2, Pre-dose	1.29 Grams per Liter Standard Deviation 5.706	-0.84 Grams per Liter Standard Deviation 5.776	—	—
Change From Baseline in Hemoglobin Chronic Day 1, Pre-dose	0.91 Grams per Liter Standard Deviation 7.596	-0.44 Grams per Liter Standard Deviation 5.973	—	—
Change From Baseline in Hemoglobin End of treatment, Pre-dose	9.13 Grams per Liter Standard Deviation 9.221	-1.42 Grams per Liter Standard Deviation 5.470	—	—
Change From Baseline in Hemoglobin Early termination	2.50 Grams per Liter Standard Deviation 2.121	—	—	—
Change From Baseline in Hemoglobin Follow-up	6.36 Grams per Liter Standard Deviation 6.350	-1.17 Grams per Liter Standard Deviation 7.786	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 39

Population: Pharmacodynamic population. Only those participants available at the specified time points were analyzed.

Blood samples for analysis of fasting levels of hematocrit was collected up to end of treatment or early termination. Baseline acute was Day 1 and Baseline chronic was Day 21. Change from Baseline was post-Baseline values minus Baseline values.

Outcome measures

Measure	GSK1278863 300 mg n=26 Participants Eligible participants received an initial single high dose of 300 mg GSK1278863 tablets orally.	Placebo Matched With GSK1278863 300 mg n=20 Participants Eligible participants received single dose of placebo matched with 300 mg GSK1278863 tablets orally.	GSK1278863 15 mg Eligible participants received repeated dose of 15 mg GSK1278863 tablets orally once daily for 14 days.	Placebo Matched With GSK1278863 15 mg Eligible participants received placebo matched with 15 mg GSK1278863 tablets orally once daily for 14 days.
Change From Baseline in Hematocrit Acute Day 2, Pre-dose	0.00 Fraction Standard Deviation 0.017	-0.00 Fraction Standard Deviation 0.018	—	—
Change From Baseline in Hematocrit Chronic Day 1, Pre-dose	0.00 Fraction Standard Deviation 0.021	0.00 Fraction Standard Deviation 0.017	—	—
Change From Baseline in Hematocrit End of treatment, Pre-dose	0.03 Fraction Standard Deviation 0.029	-0.00 Fraction Standard Deviation 0.015	—	—
Change From Baseline in Hematocrit Early termination	0.02 Fraction Standard Deviation 0.002	—	—	—
Change From Baseline in Hematocrit Follow-up	0.02 Fraction Standard Deviation 0.023	-0.00 Fraction Standard Deviation 0.023	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 39

Population: Pharmacodynamic population. Only those participants available at the specified time points were analyzed.

Blood samples for analysis of fasting levels of hsCRP, was collected up to end of treatment or early termination. Baseline acute was Day 1 and Baseline chronic was Day 21. Change from Baseline was post-Baseline values minus Baseline values.

Outcome measures

Measure	GSK1278863 300 mg n=26 Participants Eligible participants received an initial single high dose of 300 mg GSK1278863 tablets orally.	Placebo Matched With GSK1278863 300 mg n=20 Participants Eligible participants received single dose of placebo matched with 300 mg GSK1278863 tablets orally.	GSK1278863 15 mg Eligible participants received repeated dose of 15 mg GSK1278863 tablets orally once daily for 14 days.	Placebo Matched With GSK1278863 15 mg Eligible participants received placebo matched with 15 mg GSK1278863 tablets orally once daily for 14 days.
Change From Baseline in High Sensitivity C-reactive Protein (hsCRP) Acute Day 2, Pre-dose	2.51 Milligrams/Liter (mg/L) Standard Deviation 1.905	-0.08 Milligrams/Liter (mg/L) Standard Deviation 2.183	—	—
Change From Baseline in High Sensitivity C-reactive Protein (hsCRP) Chronic Day 1, Pre-dose	1.12 Milligrams/Liter (mg/L) Standard Deviation 2.909	0.21 Milligrams/Liter (mg/L) Standard Deviation 3.550	—	—
Change From Baseline in High Sensitivity C-reactive Protein (hsCRP) End of treatment, Pre-dose	1.32 Milligrams/Liter (mg/L) Standard Deviation 3.467	0.72 Milligrams/Liter (mg/L) Standard Deviation 5.625	—	—
Change From Baseline in High Sensitivity C-reactive Protein (hsCRP) Early termination	-1.50 Milligrams/Liter (mg/L) Standard Deviation 2.263	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 39

Population: Pharmacodynamic population. Only those participants available at the specified time points were analyzed.

Blood samples for analysis of fasting levels of lipid panel (TC, TG, HDLc and LDLc) was collected up to end of treatment or early termination. Baseline acute was Day 1 and Baseline chronic was Day 21. Change from Baseline was post-Baseline values minus Baseline values.

Outcome measures

Measure	GSK1278863 300 mg n=26 Participants Eligible participants received an initial single high dose of 300 mg GSK1278863 tablets orally.	Placebo Matched With GSK1278863 300 mg n=20 Participants Eligible participants received single dose of placebo matched with 300 mg GSK1278863 tablets orally.	GSK1278863 15 mg Eligible participants received repeated dose of 15 mg GSK1278863 tablets orally once daily for 14 days.	Placebo Matched With GSK1278863 15 mg Eligible participants received placebo matched with 15 mg GSK1278863 tablets orally once daily for 14 days.
Change From Baseline in Lipids (Total Cholesterol [TC], Triglycerides [TG], High Density Lipoprotein Cholesterol [HDLc] and Low Density Lipoprotein Cholesterol [LDLc]) TC: End of treatment, Pre-dose	-0.69 Millimoles/Liter (MMOL/L) Standard Deviation 0.707	0.20 Millimoles/Liter (MMOL/L) Standard Deviation 0.689	—	—
Change From Baseline in Lipids (Total Cholesterol [TC], Triglycerides [TG], High Density Lipoprotein Cholesterol [HDLc] and Low Density Lipoprotein Cholesterol [LDLc]) TC: Early termination	-0.48 Millimoles/Liter (MMOL/L) Standard Deviation 0.460	—	—	—
Change From Baseline in Lipids (Total Cholesterol [TC], Triglycerides [TG], High Density Lipoprotein Cholesterol [HDLc] and Low Density Lipoprotein Cholesterol [LDLc]) TG: End of treatment, Pre-dose	0.02 Millimoles/Liter (MMOL/L) Standard Deviation 0.835	0.27 Millimoles/Liter (MMOL/L) Standard Deviation 0.926	—	—
Change From Baseline in Lipids (Total Cholesterol [TC], Triglycerides [TG], High Density Lipoprotein Cholesterol [HDLc] and Low Density Lipoprotein Cholesterol [LDLc]) TG: Early termination	-0.52 Millimoles/Liter (MMOL/L) Standard Deviation 1.160	—	—	—
Change From Baseline in Lipids (Total Cholesterol [TC], Triglycerides [TG], High Density Lipoprotein Cholesterol [HDLc] and Low Density Lipoprotein Cholesterol [LDLc]) HDLc: End of treatment, Pre-dose	-0.17 Millimoles/Liter (MMOL/L) Standard Deviation 0.195	-0.04 Millimoles/Liter (MMOL/L) Standard Deviation 0.173	—	—
Change From Baseline in Lipids (Total Cholesterol [TC], Triglycerides [TG], High Density Lipoprotein Cholesterol [HDLc] and Low Density Lipoprotein Cholesterol [LDLc]) HDLc: Early termination	0.13 Millimoles/Liter (MMOL/L) Standard Deviation 0.177	—	—	—
Change From Baseline in Lipids (Total Cholesterol [TC], Triglycerides [TG], High Density Lipoprotein Cholesterol [HDLc] and Low Density Lipoprotein Cholesterol [LDLc]) LDLc: End of treatment, Pre-dose	-0.53 Millimoles/Liter (MMOL/L) Standard Deviation 0.489	0.12 Millimoles/Liter (MMOL/L) Standard Deviation 0.701	—	—
Change From Baseline in Lipids (Total Cholesterol [TC], Triglycerides [TG], High Density Lipoprotein Cholesterol [HDLc] and Low Density Lipoprotein Cholesterol [LDLc]) LDLc: Early termination	-0.37 Millimoles/Liter (MMOL/L) Standard Deviation 0.106	—	—	—

SECONDARY outcome

Timeframe: Visit 2 (Day 1): pre-dose, 1 hour, 2 hours and 3.5 hours post-dose, Visit 3 (Day 2)-post acute, Visit 4 (Day 16)-rescreen, Visit 5 (Day 23)-Baseline chronic and end of treatment (14 days after Visit 5) or early termination (between Visit 2 and 6)

Population: Pharmacokinetic concentration population comprised of all participants from whom a pharmacokinetic sample had been obtained and analyzed. Only those participants available at the specified time points were analyzed.

Blood samples for pharmacokinetic analysis of GSK1278863 and selected metabolites were collected at the following time points: Visit 2-Baseline acute: pre-dose, 1 hour, 2 hours and 3.5 hours post-dose, Visit 3-post acute, Visit 4-rescreen, Visit 5-Baseline chronic and end of treatment or early termination. The actual date and time of each blood sample collection was recorded.

Outcome measures

Measure	GSK1278863 300 mg n=26 Participants Eligible participants received an initial single high dose of 300 mg GSK1278863 tablets orally.	Placebo Matched With GSK1278863 300 mg n=23 Participants Eligible participants received single dose of placebo matched with 300 mg GSK1278863 tablets orally.	GSK1278863 15 mg Eligible participants received repeated dose of 15 mg GSK1278863 tablets orally once daily for 14 days.	Placebo Matched With GSK1278863 15 mg Eligible participants received placebo matched with 15 mg GSK1278863 tablets orally once daily for 14 days.
Derived Plasma GSK1278863 Pharmacokinetic Parameter- Maximum Plasma Concentration (Cmax) and Trough Concentration (Ctau) Cmax	3416.37 Nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 81.4	197.28 Nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 80.6	—	—
Derived Plasma GSK1278863 Pharmacokinetic Parameter- Maximum Plasma Concentration (Cmax) and Trough Concentration (Ctau) Ctau	6.672 Nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 131.8	1.357 Nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 19.9	—	—

SECONDARY outcome

Timeframe: Visit 2 (Day 1): pre-dose, 1 hour, 2 hours and 3.5 hours post-dose, Visit 3 (Day 2)-post acute, Visit 4 (Day 16)-rescreen, Visit 5 (Day 23)-Baseline chronic and end of treatment (14 days after Visit 5) or early termination (between Visit 2 and 6)

Population: Pharmacokinetic concentration Population. Only those participants available at the specified time points were analyzed.

Blood samples for pharmacokinetic analysis of GSK1278863 and selected metabolites were collected at the following time points: Visit 2-Baseline acute: pre-dose, 1 hour, 2 hours and 3.5 hours post-dose, Visit 3-post acute, Visit 4-rescreen, Visit 5-Baseline chronic and end of treatment or early termination. The actual date and time of each blood sample collection was recorded.

Outcome measures

Measure	GSK1278863 300 mg n=23 Participants Eligible participants received an initial single high dose of 300 mg GSK1278863 tablets orally.	Placebo Matched With GSK1278863 300 mg n=18 Participants Eligible participants received single dose of placebo matched with 300 mg GSK1278863 tablets orally.	GSK1278863 15 mg Eligible participants received repeated dose of 15 mg GSK1278863 tablets orally once daily for 14 days.	Placebo Matched With GSK1278863 15 mg Eligible participants received placebo matched with 15 mg GSK1278863 tablets orally once daily for 14 days.
Derived Plasma GSK1278863 Pharmacokinetic Parameter -Area Under the Curve (AUC [0-t])	13059.70 Nanogram x hour/milliliter (ng*h/mL) Geometric Coefficient of Variation 72.4	383.81 Nanogram x hour/milliliter (ng*h/mL) Geometric Coefficient of Variation 112.2	—	—

SECONDARY outcome

Timeframe: Visit 2 (Day 1): pre-dose, 1 hour, 2 hours and 3.5 hours post-dose, Visit 3 (Day 2)-post acute, Visit 4 (Day 16)-rescreen, Visit 5 (Day 23)-Baseline chronic and end of treatment (14 days after Visit 5) or early termination (between Visit 2 and 6)

Population: Pharmacokinetic concentration population. Only those participants available at the specified time points were analyzed.

Blood samples for pharmacokinetic analysis of GSK1278863 and selected metabolites were collected at the following time points: Visit 2-Baseline acute: pre-dose, 1 hour, 2 hours and 3.5 hours post-dose, Visit 3-post acute, Visit 4-rescreen, Visit 5-Baseline chronic and end of treatment or early termination. The actual date and time of each blood sample collection was recorded.

Outcome measures

Measure	GSK1278863 300 mg n=26 Participants Eligible participants received an initial single high dose of 300 mg GSK1278863 tablets orally.	Placebo Matched With GSK1278863 300 mg n=23 Participants Eligible participants received single dose of placebo matched with 300 mg GSK1278863 tablets orally.	GSK1278863 15 mg Eligible participants received repeated dose of 15 mg GSK1278863 tablets orally once daily for 14 days.	Placebo Matched With GSK1278863 15 mg Eligible participants received placebo matched with 15 mg GSK1278863 tablets orally once daily for 14 days.
Derived Plasma GSK1278863 Pharmacokinetic Parameter - Time to Maximum Plasma Concentration (T-max) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) Tmax	1.016 Hour Interval 0.85 to 3.667	1.000 Hour Interval 0.833 to 3.583	—	—
Derived Plasma GSK1278863 Pharmacokinetic Parameter - Time to Maximum Plasma Concentration (T-max) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) Tlast	22.417 Hour Interval 3.42 to 24.47	3.500 Hour Interval 3.37 to 23.08	—	—

SECONDARY outcome

Timeframe: Visit 2 (Day 1): pre-dose, 1 hour, 2 hours and 3.5 hours post-dose, Visit 3 (Day 2)-post acute, Visit 4 (Day 16)-rescreen, Visit 5 (Day 23)-Baseline chronic and end of treatment (14 days after Visit 5) or early termination (between Visit 2 and 6)

Population: The data for this outcome measure was not collected.

A formal pharmacokinetic /pharmacodynamic analysis and pharmacokinetic /pharmacodynamic modelling for exposure relationships to endpoints was planned. The data for this outcome was not collected.

Outcome measures

Outcome data not reported

Adverse Events

GSK1278863 300 mg

Serious events: 2 serious events

Other events: 10 other events

Deaths: 0 deaths

Placebo Matched With GSK1278863 300 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

GSK1278863 15 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Placebo Matched With GSK1278863 15 mg

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	GSK1278863 300 mg n=26 participants at risk Eligible participants received an initial single high dose of 300 mg GSK1278863 tablets orally.	Placebo Matched With GSK1278863 300 mg n=20 participants at risk Eligible participants received single dose of placebo matched with 300 mg GSK1278863 tablets orally.	GSK1278863 15 mg n=23 participants at risk Eligible participants received repeated dose of 15 mg GSK1278863 tablets orally once daily for 14 days.	Placebo Matched With GSK1278863 15 mg n=19 participants at risk Eligible participants received placebo matched with 15 mg GSK1278863 tablets orally for 14 days.
Cardiac disorders Atrial fibrillation	3.8% 1/26 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/20 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/23 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/19 • Up to 67 days. SAE and non-SAE were reported for the Safety population.
Cardiac disorders Cardiac failure congestive	3.8% 1/26 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/20 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/23 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/19 • Up to 67 days. SAE and non-SAE were reported for the Safety population.
Metabolism and nutrition disorders Hyponatraemia	3.8% 1/26 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/20 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/23 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/19 • Up to 67 days. SAE and non-SAE were reported for the Safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lip and/or oral cavity cancer	3.8% 1/26 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/20 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/23 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/19 • Up to 67 days. SAE and non-SAE were reported for the Safety population.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	3.8% 1/26 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/20 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/23 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/19 • Up to 67 days. SAE and non-SAE were reported for the Safety population.
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/26 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/20 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/23 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	5.3% 1/19 • Up to 67 days. SAE and non-SAE were reported for the Safety population.

Other adverse events

Measure	GSK1278863 300 mg n=26 participants at risk Eligible participants received an initial single high dose of 300 mg GSK1278863 tablets orally.	Placebo Matched With GSK1278863 300 mg n=20 participants at risk Eligible participants received single dose of placebo matched with 300 mg GSK1278863 tablets orally.	GSK1278863 15 mg n=23 participants at risk Eligible participants received repeated dose of 15 mg GSK1278863 tablets orally once daily for 14 days.	Placebo Matched With GSK1278863 15 mg n=19 participants at risk Eligible participants received placebo matched with 15 mg GSK1278863 tablets orally for 14 days.
Gastrointestinal disorders Diarrhoea	11.5% 3/26 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/20 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/23 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/19 • Up to 67 days. SAE and non-SAE were reported for the Safety population.
Gastrointestinal disorders Dyspepsia	7.7% 2/26 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/20 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/23 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/19 • Up to 67 days. SAE and non-SAE were reported for the Safety population.
Gastrointestinal disorders Flatulence	0.00% 0/26 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	5.0% 1/20 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/23 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/19 • Up to 67 days. SAE and non-SAE were reported for the Safety population.
Gastrointestinal disorders Paraesthesia oral	0.00% 0/26 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	5.0% 1/20 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/23 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/19 • Up to 67 days. SAE and non-SAE were reported for the Safety population.
Infections and infestations Nasopharyngitis	0.00% 0/26 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	5.0% 1/20 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	4.3% 1/23 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/19 • Up to 67 days. SAE and non-SAE were reported for the Safety population.
Infections and infestations Upper respiratory tract infection	7.7% 2/26 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/20 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/23 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/19 • Up to 67 days. SAE and non-SAE were reported for the Safety population.
Infections and infestations Cellulitis	0.00% 0/26 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	5.0% 1/20 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/23 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/19 • Up to 67 days. SAE and non-SAE were reported for the Safety population.
Infections and infestations Sinusitis	0.00% 0/26 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	5.0% 1/20 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/23 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/19 • Up to 67 days. SAE and non-SAE were reported for the Safety population.
Musculoskeletal and connective tissue disorders Pain in extremity	11.5% 3/26 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/20 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	8.7% 2/23 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/19 • Up to 67 days. SAE and non-SAE were reported for the Safety population.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/26 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/20 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/23 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	5.3% 1/19 • Up to 67 days. SAE and non-SAE were reported for the Safety population.
General disorders Fatigue	7.7% 2/26 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/20 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/23 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/19 • Up to 67 days. SAE and non-SAE were reported for the Safety population.
General disorders Oedema peripheral	0.00% 0/26 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/20 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/23 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	5.3% 1/19 • Up to 67 days. SAE and non-SAE were reported for the Safety population.
Nervous system disorders Somnolence	3.8% 1/26 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	5.0% 1/20 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/23 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/19 • Up to 67 days. SAE and non-SAE were reported for the Safety population.
Nervous system disorders Headache	0.00% 0/26 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	5.0% 1/20 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/23 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/19 • Up to 67 days. SAE and non-SAE were reported for the Safety population.
Nervous system disorders Hyperaesthesia	0.00% 0/26 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/20 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/23 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	5.3% 1/19 • Up to 67 days. SAE and non-SAE were reported for the Safety population.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/26 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	5.0% 1/20 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/23 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/19 • Up to 67 days. SAE and non-SAE were reported for the Safety population.
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/26 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/20 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	0.00% 0/23 • Up to 67 days. SAE and non-SAE were reported for the Safety population.	5.3% 1/19 • Up to 67 days. SAE and non-SAE were reported for the Safety population.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

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

Restriction type: OTHER