Trial Outcomes & Findings for Study to Test GSK256073 in Patients With Dyslipidemia (NCT NCT00903617)

Last Updated: 2019-12-05

Results Overview

The potential PK/PD relationship was to be assessed by plotting GSK256073 AUCs against HDLc. The PK/PD model that was to be used for the simulations in the study design was to be refined with the Part A observed AUC exposures and HDLc levels. However, the study was stopped for futility at the end of Part A due to lack of a compelling PK/PD relationship between GSK256073 and lipid effects that would predict success in achieving significant HDLc raising.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

80 participants

Primary outcome timeframe

Week 2, 4, 6 and 8

Results posted on

2019-12-05

Participant Flow

This study was conducted at 11 centers in the United States from 15 June 2009 to 16 February 2010.

A total of 80 participant were enrolled in the study. Participants on lipid-altering medications (prescription, over-the-counter and herbal preparations directed at lipid lowering) were washed out of their treatment for at least 6 weeks prior to randomization and 8 weeks wash out for participants on fibrate medications.

Participant milestones

Participant milestones
Measure	GSK256073 5 mg Eligible participants received GSK256073 5 milligrams (mg) oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 50 mg Eligible participants received GSK256073 50 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 150 mg Eligible participants received GSK256073 150 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	Placebo Eligible participants received placebo matching GSK256073 oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.
Overall Study STARTED	19	20	20	21
Overall Study COMPLETED	16	15	15	20
Overall Study NOT COMPLETED	3	5	5	1

Reasons for withdrawal

Reasons for withdrawal
Measure	GSK256073 5 mg Eligible participants received GSK256073 5 milligrams (mg) oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 50 mg Eligible participants received GSK256073 50 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 150 mg Eligible participants received GSK256073 150 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	Placebo Eligible participants received placebo matching GSK256073 oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.
Overall Study Adverse Event	0	1	1	0
Overall Study Protocol-defined stopping criteria	0	2	0	0
Overall Study Lost to Follow-up	2	0	1	1
Overall Study Withdrawal by Subject	1	2	3	0

Baseline Characteristics

Study to Test GSK256073 in Patients With Dyslipidemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GSK256073 5 mg n=19 Participants Eligible participants received GSK256073 5 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 50 mg n=20 Participants Eligible participants received GSK256073 50 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 150 mg n=20 Participants Eligible participants received GSK256073 150 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	Placebo n=21 Participants Eligible participants received placebo matching GSK256073 oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	Total n=80 Participants Total of all reporting groups
Age, Continuous	58.3 Years STANDARD_DEVIATION 8.43 • n=5 Participants	53.8 Years STANDARD_DEVIATION 9.77 • n=7 Participants	57.0 Years STANDARD_DEVIATION 10.75 • n=5 Participants	57.7 Years STANDARD_DEVIATION 10.15 • n=4 Participants	56.7 Years STANDARD_DEVIATION 9.80 • n=21 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	10 Participants n=7 Participants	10 Participants n=5 Participants	11 Participants n=4 Participants	41 Participants n=21 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	10 Participants n=7 Participants	10 Participants n=5 Participants	10 Participants n=4 Participants	39 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	6 Participants n=21 Participants
Race (NIH/OMB) White	18 Participants n=5 Participants	18 Participants n=7 Participants	19 Participants n=5 Participants	18 Participants n=4 Participants	73 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: Week 2, 4, 6 and 8

Population: Data was not collected as the study was stopped for futility at the end of Part A due to lack of a compelling PK/PD relationship between GSK256073 and lipid effects that would predict success in achieving significant HDLc raising.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to follow up (14 days from last dose)

Population: Safety Population was defined as all participants who received at least one dose of study drug.

An AE is any untoward medical occurrence in a 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, medically significant or it is associated with liver injury and impaired liver function.

Outcome measures

Outcome measures
Measure	GSK256073 5 mg n=19 Participants Eligible participants received GSK256073 5 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 50 mg n=20 Participants Eligible participants received GSK256073 50 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 150 mg n=20 Participants Eligible participants received GSK256073 150 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	Placebo n=21 Participants Eligible participants received placebo matching GSK256073 oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AEs	8 Participants	12 Participants	17 Participants	14 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any SAEs	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 8

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

Single 12-lead ECGs was obtained at each time point during the study using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QTc intervals. Participants with normal, abnormal- clinically significant (CS) and abnormal- not clinically significant (NCS) ECG values were reported.

Outcome measures

Outcome measures
Measure	GSK256073 5 mg n=19 Participants Eligible participants received GSK256073 5 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 50 mg n=20 Participants Eligible participants received GSK256073 50 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 150 mg n=20 Participants Eligible participants received GSK256073 150 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	Placebo n=21 Participants Eligible participants received placebo matching GSK256073 oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.
Number of Participants With Electrocardiography (ECG) Findings Baseline, Predose, Normal	9 Participants	5 Participants	8 Participants	13 Participants
Number of Participants With Electrocardiography (ECG) Findings Baseline, Predose, Abnormal-CS	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiography (ECG) Findings Week 2, Predose, Normal	10 Participants	10 Participants	9 Participants	13 Participants
Number of Participants With Electrocardiography (ECG) Findings Week 2, Predose, Abnormal-CS	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiography (ECG) Findings Baseline, Predose, Abnormal-NCS	10 Participants	15 Participants	12 Participants	8 Participants
Number of Participants With Electrocardiography (ECG) Findings Week 2, Predose, Abnormal-NCS	8 Participants	9 Participants	10 Participants	7 Participants
Number of Participants With Electrocardiography (ECG) Findings Week 4, Predose, Normal	8 Participants	5 Participants	10 Participants	16 Participants
Number of Participants With Electrocardiography (ECG) Findings Week 4, Predose, Abnormal-NCS	9 Participants	12 Participants	8 Participants	4 Participants
Number of Participants With Electrocardiography (ECG) Findings Week 4, Predose, Abnormal-CS	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiography (ECG) Findings Week 6, Predose, Normal	9 Participants	4 Participants	10 Participants	15 Participants
Number of Participants With Electrocardiography (ECG) Findings Week 6, Predose, Abnormal-CS	7 Participants	12 Participants	6 Participants	5 Participants
Number of Participants With Electrocardiography (ECG) Findings Week 6, Predose, Abnormal-NCS	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiography (ECG) Findings Week 8, 0 hour, Normal	10 Participants	5 Participants	9 Participants	13 Participants
Number of Participants With Electrocardiography (ECG) Findings Week 8, 0 hour, Abnormal-NCS	6 Participants	10 Participants	6 Participants	7 Participants
Number of Participants With Electrocardiography (ECG) Findings Week 8, 0 hour, Abnormal-CS	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Week 0) up to Week 8

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

SBP and DBP was assessed at Baseline (Week 0), Week 2, 4, 6 and 8. Baseline was defined at Week 0. Change from Baseline was calculated by subtracting the post-Baseline value from the Baseline value.

Outcome measures

Outcome measures
Measure	GSK256073 5 mg n=19 Participants Eligible participants received GSK256073 5 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 50 mg n=20 Participants Eligible participants received GSK256073 50 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 150 mg n=20 Participants Eligible participants received GSK256073 150 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	Placebo n=21 Participants Eligible participants received placebo matching GSK256073 oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.
Change From Baseline in Vital Signs-Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 8, 0 hour	1.8 Millimeters of mercury (mmHg) Standard Deviation 10.64	1.0 Millimeters of mercury (mmHg) Standard Deviation 13.96	-1.3 Millimeters of mercury (mmHg) Standard Deviation 8.35	0.8 Millimeters of mercury (mmHg) Standard Deviation 9.00
Change From Baseline in Vital Signs-Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 2, 0 hour	-2.1 Millimeters of mercury (mmHg) Standard Deviation 6.39	-0.1 Millimeters of mercury (mmHg) Standard Deviation 4.93	-1.0 Millimeters of mercury (mmHg) Standard Deviation 3.42	1.1 Millimeters of mercury (mmHg) Standard Deviation 4.86
Change From Baseline in Vital Signs-Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 4, 0 hour	-2.6 Millimeters of mercury (mmHg) Standard Deviation 3.97	0.8 Millimeters of mercury (mmHg) Standard Deviation 7.12	0.8 Millimeters of mercury (mmHg) Standard Deviation 3.61	1.6 Millimeters of mercury (mmHg) Standard Deviation 5.35
Change From Baseline in Vital Signs-Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 6, 0 hour	-0.6 Millimeters of mercury (mmHg) Standard Deviation 5.37	-1.3 Millimeters of mercury (mmHg) Standard Deviation 7.53	1.6 Millimeters of mercury (mmHg) Standard Deviation 5.51	1.4 Millimeters of mercury (mmHg) Standard Deviation 5.28
Change From Baseline in Vital Signs-Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Week 8, 0 hour	0.8 Millimeters of mercury (mmHg) Standard Deviation 6.41	-1.7 Millimeters of mercury (mmHg) Standard Deviation 8.47	2.0 Millimeters of mercury (mmHg) Standard Deviation 6.89	1.9 Millimeters of mercury (mmHg) Standard Deviation 5.43
Change From Baseline in Vital Signs-Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 2, 0 hour	-3.0 Millimeters of mercury (mmHg) Standard Deviation 11.03	2.7 Millimeters of mercury (mmHg) Standard Deviation 9.91	-2.7 Millimeters of mercury (mmHg) Standard Deviation 5.54	2.1 Millimeters of mercury (mmHg) Standard Deviation 9.25
Change From Baseline in Vital Signs-Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 4, 0 hour	-4.5 Millimeters of mercury (mmHg) Standard Deviation 11.27	6.1 Millimeters of mercury (mmHg) Standard Deviation 11.74	-3.2 Millimeters of mercury (mmHg) Standard Deviation 5.17	4.2 Millimeters of mercury (mmHg) Standard Deviation 9.46
Change From Baseline in Vital Signs-Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Week 6, 0 hour	3.7 Millimeters of mercury (mmHg) Standard Deviation 9.86	0.9 Millimeters of mercury (mmHg) Standard Deviation 12.12	-0.1 Millimeters of mercury (mmHg) Standard Deviation 10.21	0.2 Millimeters of mercury (mmHg) Standard Deviation 9.29

SECONDARY outcome

Timeframe: Baseline (Week 0) up to Week 8

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

Heart rate was assessed at Baseline (Week 0), Week 2, 4, 6 and 8. Baseline was defined at Week 0. Change from Baseline was calculated by subtracting the post-Baseline value from the Baseline value.

Outcome measures

Outcome measures
Measure	GSK256073 5 mg n=19 Participants Eligible participants received GSK256073 5 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 50 mg n=20 Participants Eligible participants received GSK256073 50 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 150 mg n=20 Participants Eligible participants received GSK256073 150 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	Placebo n=21 Participants Eligible participants received placebo matching GSK256073 oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.
Change From Baseline in Vital Signs-Heart Rate Week 8, 0 hour	0.0 Beats per minute Standard Deviation 7.25	3.5 Beats per minute Standard Deviation 4.37	4.6 Beats per minute Standard Deviation 5.87	2.2 Beats per minute Standard Deviation 4.53
Change From Baseline in Vital Signs-Heart Rate Week 2, 0 hour	1.4 Beats per minute Standard Deviation 8.14	-0.5 Beats per minute Standard Deviation 7.17	1.9 Beats per minute Standard Deviation 4.21	1.1 Beats per minute Standard Deviation 4.20
Change From Baseline in Vital Signs-Heart Rate Week 4, 0 hour	-1.2 Beats per minute Standard Deviation 4.82	-1.9 Beats per minute Standard Deviation 5.61	3.6 Beats per minute Standard Deviation 4.83	1.9 Beats per minute Standard Deviation 5.31
Change From Baseline in Vital Signs-Heart Rate Week 6, 0 hour	-1.4 Beats per minute Standard Deviation 6.85	-0.2 Beats per minute Standard Deviation 5.96	2.8 Beats per minute Standard Deviation 4.97	3.6 Beats per minute Standard Deviation 5.61

SECONDARY outcome

Timeframe: Baseline (Week 0) up to Week 8

Population: Safety Population.

Blood samples for assessment of hematology parameters of platelet count, red blood cell count, white blood cell count, hemoglobin, haptoglobin, reticulocyte count, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, neutrophils, lymphocytes, monocytes, eosinophils and basophils was collected at Baseline and at Weeks 2, 4, 6 and 8.

Outcome measures

Outcome measures
Measure	GSK256073 5 mg n=19 Participants Eligible participants received GSK256073 5 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 50 mg n=20 Participants Eligible participants received GSK256073 50 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 150 mg n=20 Participants Eligible participants received GSK256073 150 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	Placebo n=21 Participants Eligible participants received placebo matching GSK256073 oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.
Number of Participants With Abnormal Hematology Values	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 8

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

Blood samples for assessment of clinical chemistry parameters of blood urea nitrogen, creatinine, glucose (fasting), sodium, creatine phosphokinase, potassium, chloride, total carbon dioxide, calcium, total lactose dehydrogenase (LDH), aspartate aminotransferase (AST), alanine amino transferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase, phosphate, total and direct bilirubin, uric acid, albumin and total protein was collected at Baseline and at Weeks 2, 4, 6 and 8.

Outcome measures

Outcome measures
Measure	GSK256073 5 mg n=19 Participants Eligible participants received GSK256073 5 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 50 mg n=20 Participants Eligible participants received GSK256073 50 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 150 mg n=20 Participants Eligible participants received GSK256073 150 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	Placebo n=21 Participants Eligible participants received placebo matching GSK256073 oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.
Number of Participants With Abnormal Clinical Chemistry Values Creatine kinase, Week 6, High	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Clinical Chemistry Values Phosphorous, inorganic, Week 8, low	1 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 8

Population: Safety Population.

Urinalysis assessment was done for urine occult blood, urine glucose, urine ketones and urine protein over eight weeks treatment period.

Outcome measures

Outcome measures
Measure	GSK256073 5 mg n=19 Participants Eligible participants received GSK256073 5 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 50 mg n=20 Participants Eligible participants received GSK256073 50 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 150 mg n=20 Participants Eligible participants received GSK256073 150 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	Placebo n=21 Participants Eligible participants received placebo matching GSK256073 oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.
Number of Participants With Abnormal Urinalysis Results Urine Occult Blood, Week 2, Predose, Trace	0 Participants	2 Participants	0 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Results Urine Protein, Week 8, 0 hour, 1+	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Results Urine Occult Blood, Baseline, Predose, 1+	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Results Urine Occult Blood, Baseline, Predose, Trace	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Results Urine Occult Blood, Week 2, Predose, 1+	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Results Urine Occult Blood, Week 4, Predose, 1+	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Results Urine Occult Blood, Week 4, Predose, Trace	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Results Urine Occult Blood, Week 6, Predose, 3+	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Results Urine Occult Blood, Week 6, Predose, Trace	0 Participants	2 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Results Urine Occult Blood, Week 8, 0 hour, 1+	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Results Urine Occult Blood, Week 8, 0 hour, Trace	0 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Results Urine Ketones, Baseline, Predose, Trace	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Results Urine Ketones, Week 2, Predose, Trace	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Results Urine Ketones, Week 4, Predose, 2+	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Results Urine Ketones, Week 6, Predose, Trace	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Results Urine Ketones, Week 8, 0 hour, 1+	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Results Urine Protein, Baseline, Predose, Trace	0 Participants	1 Participants	1 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Results Urine Protein, Week 2, Predose, Trace	1 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Results Urine Protein, Week 4, Predose, 1+	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Results Urine Protein, Week 4, Predose, Trace	0 Participants	1 Participants	2 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Results Urine Protein, Week 6, Predose, 1+	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Results Urine Protein, Week 6, Predose, Trace	1 Participants	1 Participants	1 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Results Urine Protein, Week 8, 0 hour, Trace	1 Participants	0 Participants	3 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to Week 8

Population: PD Population.

Flushing assessment was captured by participants in individual diaries provided to each study participant. Participants were instructed to return their diaries after each study visit (Week 2, Week 4, Week 6 and Week 8) where they were given a new diary for the time between visits. Flushing symptom questionnaire (FSQ) was used to measure participant reported feelings of severity associated with different types of flushing symptoms. The FSQ comprised of 11 items. The response scale combined verbal descriptors as well as a 0-10 numerical rating scale. Items 1, 2, 4 and 10 had verbal descriptors. The items 3, 5, 6, 7, 8, 9 and 11 were rated on a 0 to 10 scale (none=0, mild=1-3, moderate=4-6, severe=7-9 and extreme=10). The total score for these items ranged from 0 (not at all) to 70 (extreme). Higher score indicated more severe flushing symptoms and 0 indicated no flushing symptoms.

Outcome measures

Outcome measures
Measure	GSK256073 5 mg n=19 Participants Eligible participants received GSK256073 5 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 50 mg n=20 Participants Eligible participants received GSK256073 50 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 150 mg n=20 Participants Eligible participants received GSK256073 150 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	Placebo n=21 Participants Eligible participants received placebo matching GSK256073 oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.
Average Global Flushing Score Severe	0 Participants	0 Participants	0 Participants	1 Participants
Average Global Flushing Score None	15 Participants	16 Participants	8 Participants	15 Participants
Average Global Flushing Score Mild	2 Participants	2 Participants	8 Participants	4 Participants
Average Global Flushing Score Moderate	1 Participants	2 Participants	4 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 8

Population: PD Population.

Flushing assessment was captured by participants in individual diaries provided to each study participant. Participants were instructed to return their diaries after each study visit (Week 2, Week 4, Week 6 and Week 8) where they were given a new diary for the time between visits. Participants were asked to perform an assessment of their perceived flushing intensity after their completion of VAS assessment once daily after their first flushing episode (if more than one happens to occur). The scale was from 0 to 3, where 0 represents no flushing, 1 represents mild flushing, 2 represents moderate flushing, and 3 represents severe flushing.

Outcome measures

Outcome measures
Measure	GSK256073 5 mg n=19 Participants Eligible participants received GSK256073 5 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 50 mg n=20 Participants Eligible participants received GSK256073 50 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 150 mg n=20 Participants Eligible participants received GSK256073 150 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	Placebo n=21 Participants Eligible participants received placebo matching GSK256073 oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.
Number of Participants With Self Reported Assessment of Flushing Baseline, Mild flushing	1 Participants	1 Participants	6 Participants	0 Participants
Number of Participants With Self Reported Assessment of Flushing Week 2, Mild flushing	1 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Self Reported Assessment of Flushing Baseline, No flushing	17 Participants	14 Participants	9 Participants	18 Participants
Number of Participants With Self Reported Assessment of Flushing Week 2, No flushing	15 Participants	17 Participants	18 Participants	19 Participants
Number of Participants With Self Reported Assessment of Flushing Week 4, No flushing	12 Participants	17 Participants	15 Participants	20 Participants
Number of Participants With Self Reported Assessment of Flushing Week 6, No flushing	14 Participants	14 Participants	14 Participants	20 Participants
Number of Participants With Self Reported Assessment of Flushing Week 4, Mild flushing	1 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Self Reported Assessment of Flushing Week 6, Mild flushing	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Self Reported Assessment of Flushing Baseline, Moderate flushing	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Self Reported Assessment of Flushing Baseline, Severe flushing	0 Participants	0 Participants	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 8

Population: PD Population.

Outcome measures

Outcome measures
Measure	GSK256073 5 mg n=19 Participants Eligible participants received GSK256073 5 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 50 mg n=20 Participants Eligible participants received GSK256073 50 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 150 mg n=20 Participants Eligible participants received GSK256073 150 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	Placebo n=21 Participants Eligible participants received placebo matching GSK256073 oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.
Average Number of Flushing Episodes 2 flushing episode	0 Participants	2 Participants	3 Participants	3 Participants
Average Number of Flushing Episodes Did not have flushing episodes	15 Participants	16 Participants	8 Participants	15 Participants
Average Number of Flushing Episodes 1 flushing episode	3 Participants	1 Participants	9 Participants	1 Participants
Average Number of Flushing Episodes 3 or more flushing episode	0 Participants	1 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to Week 8

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

Outcome measures

Outcome measures
Measure	GSK256073 5 mg n=3 Participants Eligible participants received GSK256073 5 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 50 mg n=4 Participants Eligible participants received GSK256073 50 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 150 mg n=12 Participants Eligible participants received GSK256073 150 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	Placebo n=5 Participants Eligible participants received placebo matching GSK256073 oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.
Average Time to Onset of Flushing	9.1 Hours Interval 6.0 to 13.0	3.6 Hours Interval 0.0 to 12.0	1.0 Hours Interval 0.0 to 9.0	4.1 Hours Interval 0.0 to 20.0

SECONDARY outcome

Timeframe: Up to Week 8

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

Outcome measures

Outcome measures
Measure	GSK256073 5 mg n=3 Participants Eligible participants received GSK256073 5 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 50 mg n=4 Participants Eligible participants received GSK256073 50 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 150 mg n=12 Participants Eligible participants received GSK256073 150 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	Placebo n=5 Participants Eligible participants received placebo matching GSK256073 oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.
Participant's Average Duration of Flushing	36.7 Minutes Interval 5.0 to 90.0	151.7 Minutes Interval 113.0 to 393.0	60.0 Minutes Interval 4.0 to 160.0	72.1 Minutes Interval 5.0 to 149.0

SECONDARY outcome

Timeframe: Up to follow up (14 days from last dose)

Population: Safety Population.

Outcome measures

Outcome measures
Measure	GSK256073 5 mg n=19 Participants Eligible participants received GSK256073 5 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 50 mg n=20 Participants Eligible participants received GSK256073 50 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 150 mg n=20 Participants Eligible participants received GSK256073 150 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	Placebo n=21 Participants Eligible participants received placebo matching GSK256073 oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.
Number of Participants Who Withdrew Due to Flushing	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 8

Population: PD Population was defined as all participants who provided PD data.

Flushing assessment was captured by participants in individual diaries provided to each study participant. Participants were instructed to return their diaries after each study visit (Week 2, Week 4, Week 6 and Week 8) where they were given a new diary for the time between visits. Participants self-assessed intensity of flushing using a 100 mm VAS once daily at the first flushing episode. The left hand side of the scale (0) represented 'No Flushing Sensation' and the right hand side of the scale (100) represented 'Unbearable Flushing Sensation'. The intensity of flushing of each episode was measured in centimeters (to the nearest 1/100) from the 0 point of the scale. Data is reported for average VAS scores over 8 weeks of treatment.

Outcome measures

Outcome measures
Measure	GSK256073 5 mg n=4 Participants Eligible participants received GSK256073 5 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 50 mg n=4 Participants Eligible participants received GSK256073 50 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 150 mg n=12 Participants Eligible participants received GSK256073 150 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	Placebo n=6 Participants Eligible participants received placebo matching GSK256073 oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.
Mean Episode of Flushing as Measured by Visual Analogue Scale (VAS)	9.0 Scores on a scale Standard Deviation 9.58	31.8 Scores on a scale Standard Deviation 19.24	24.9 Scores on a scale Standard Deviation 15.14	17.1 Scores on a scale Standard Deviation 26.76

SECONDARY outcome

Timeframe: Baseline (Week 0) up to Week 8

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

Blood samples for analysis of fasting levels of HDLc and ApoA1 was collected at Baseline (Week 0) and Week 2, 4, 6 and 8. Baseline was defined at Week 0. Change from Baseline was calculated by subtracting the post-Baseline value from the Baseline value. Percent change from Baseline was calculated by multiplying change from baseline value with 100.

Outcome measures

Outcome measures
Measure	GSK256073 5 mg n=19 Participants Eligible participants received GSK256073 5 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 50 mg n=20 Participants Eligible participants received GSK256073 50 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 150 mg n=20 Participants Eligible participants received GSK256073 150 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	Placebo n=21 Participants Eligible participants received placebo matching GSK256073 oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.
Percent Change From Baseline in Fasting Plasma HDLc and Apolipoprotein A-I (ApoA1) Concentrations Over Eight Weeks of Administration With GSK256073 or Placebo HDLc, Week 4	-1.2 Percent change Standard Deviation 7.60	-4.6 Percent change Standard Deviation 19.54	-7.0 Percent change Standard Deviation 17.24	-1.3 Percent change Standard Deviation 8.00
Percent Change From Baseline in Fasting Plasma HDLc and Apolipoprotein A-I (ApoA1) Concentrations Over Eight Weeks of Administration With GSK256073 or Placebo ApoA1, Week 2	-2.7 Percent change Standard Deviation 10.47	-5.7 Percent change Standard Deviation 15.45	-5.9 Percent change Standard Deviation 8.53	-2.2 Percent change Standard Deviation 8.63
Percent Change From Baseline in Fasting Plasma HDLc and Apolipoprotein A-I (ApoA1) Concentrations Over Eight Weeks of Administration With GSK256073 or Placebo ApoA1, Week 4	1.4 Percent change Standard Deviation 8.73	-1.8 Percent change Standard Deviation 11.55	-6.5 Percent change Standard Deviation 11.01	1.3 Percent change Standard Deviation 9.85
Percent Change From Baseline in Fasting Plasma HDLc and Apolipoprotein A-I (ApoA1) Concentrations Over Eight Weeks of Administration With GSK256073 or Placebo ApoA1, Week 6	0.6 Percent change Standard Deviation 14.23	-3.1 Percent change Standard Deviation 8.96	-1.1 Percent change Standard Deviation 9.75	-1.3 Percent change Standard Deviation 8.73
Percent Change From Baseline in Fasting Plasma HDLc and Apolipoprotein A-I (ApoA1) Concentrations Over Eight Weeks of Administration With GSK256073 or Placebo ApoA1, Week 8	4.2 Percent change Standard Deviation 10.48	-0.2 Percent change Standard Deviation 13.50	-2.0 Percent change Standard Deviation 9.38	0.3 Percent change Standard Deviation 9.25
Percent Change From Baseline in Fasting Plasma HDLc and Apolipoprotein A-I (ApoA1) Concentrations Over Eight Weeks of Administration With GSK256073 or Placebo HDLc, Week 2	-2.2 Percent change Standard Deviation 10.50	-8.4 Percent change Standard Deviation 14.82	-9.4 Percent change Standard Deviation 13.76	-2.8 Percent change Standard Deviation 7.54
Percent Change From Baseline in Fasting Plasma HDLc and Apolipoprotein A-I (ApoA1) Concentrations Over Eight Weeks of Administration With GSK256073 or Placebo HDLc, Week 6	-2.0 Percent change Standard Deviation 11.76	-4.9 Percent change Standard Deviation 12.80	-7.9 Percent change Standard Deviation 13.66	0.2 Percent change Standard Deviation 11.17
Percent Change From Baseline in Fasting Plasma HDLc and Apolipoprotein A-I (ApoA1) Concentrations Over Eight Weeks of Administration With GSK256073 or Placebo HDLc, Week 8	4.2 Percent change Standard Deviation 12.99	-1.9 Percent change Standard Deviation 13.32	-9.1 Percent change Standard Deviation 15.46	1.1 Percent change Standard Deviation 9.72

SECONDARY outcome

Timeframe: Baseline (Week 0) up to Week 8

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

Blood samples for analysis of fasting levels of TC, TG, glucose, LDLc, ApoAII and ApoB was collected at Baseline (Week 0) and Week 2, 4, 6 and 8. Baseline was defined at Week 0. Change from Baseline was calculated by subtracting the post-Baseline value from the Baseline value. Percent change from Baseline was calculated by multiplying change from baseline value with 100.

Outcome measures

Outcome measures
Measure	GSK256073 5 mg n=19 Participants Eligible participants received GSK256073 5 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 50 mg n=20 Participants Eligible participants received GSK256073 50 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 150 mg n=20 Participants Eligible participants received GSK256073 150 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	Placebo n=21 Participants Eligible participants received placebo matching GSK256073 oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.
Percent Change From Baseline in Fasting Levels of Total Cholesterol (TC), Triglyceride (TG), Glucose, Low Density Lipoprotein Cholesterol (LDLc), Apolipoprotein A2 (ApoAII), Apolipoprotein B (ApoB) Over 8 Weeks of Administration With GSK256073 or Placebo TG, Week 4	6.1 Percent change Standard Deviation 26.36	10.1 Percent change Standard Deviation 55.36	3.0 Percent change Standard Deviation 27.41	3.5 Percent change Standard Deviation 24.63
Percent Change From Baseline in Fasting Levels of Total Cholesterol (TC), Triglyceride (TG), Glucose, Low Density Lipoprotein Cholesterol (LDLc), Apolipoprotein A2 (ApoAII), Apolipoprotein B (ApoB) Over 8 Weeks of Administration With GSK256073 or Placebo TG, Week 6	7.5 Percent change Standard Deviation 21.81	0.9 Percent change Standard Deviation 38.38	8.4 Percent change Standard Deviation 23.84	-4.6 Percent change Standard Deviation 16.82
Percent Change From Baseline in Fasting Levels of Total Cholesterol (TC), Triglyceride (TG), Glucose, Low Density Lipoprotein Cholesterol (LDLc), Apolipoprotein A2 (ApoAII), Apolipoprotein B (ApoB) Over 8 Weeks of Administration With GSK256073 or Placebo TG, Week 8	6.6 Percent change Standard Deviation 34.96	5.6 Percent change Standard Deviation 41.75	21.0 Percent change Standard Deviation 28.14	-4.0 Percent change Standard Deviation 17.76
Percent Change From Baseline in Fasting Levels of Total Cholesterol (TC), Triglyceride (TG), Glucose, Low Density Lipoprotein Cholesterol (LDLc), Apolipoprotein A2 (ApoAII), Apolipoprotein B (ApoB) Over 8 Weeks of Administration With GSK256073 or Placebo ApoAII, Week 2	-9.9 Percent change Standard Deviation 14.51	-6.9 Percent change Standard Deviation 13.60	-4.7 Percent change Standard Deviation 7.56	0.1 Percent change Standard Deviation 17.22
Percent Change From Baseline in Fasting Levels of Total Cholesterol (TC), Triglyceride (TG), Glucose, Low Density Lipoprotein Cholesterol (LDLc), Apolipoprotein A2 (ApoAII), Apolipoprotein B (ApoB) Over 8 Weeks of Administration With GSK256073 or Placebo ApoAII, Week 4	7.2 Percent change Standard Deviation 38.06	3.4 Percent change Standard Deviation 28.15	-3.8 Percent change Standard Deviation 11.36	-1.6 Percent change Standard Deviation 10.98
Percent Change From Baseline in Fasting Levels of Total Cholesterol (TC), Triglyceride (TG), Glucose, Low Density Lipoprotein Cholesterol (LDLc), Apolipoprotein A2 (ApoAII), Apolipoprotein B (ApoB) Over 8 Weeks of Administration With GSK256073 or Placebo ApoAII, Week 6	5.9 Percent change Standard Deviation 29.61	-7.0 Percent change Standard Deviation 10.96	-5.3 Percent change Standard Deviation 9.16	2.0 Percent change Standard Deviation 15.60
Percent Change From Baseline in Fasting Levels of Total Cholesterol (TC), Triglyceride (TG), Glucose, Low Density Lipoprotein Cholesterol (LDLc), Apolipoprotein A2 (ApoAII), Apolipoprotein B (ApoB) Over 8 Weeks of Administration With GSK256073 or Placebo ApoAII, Week 8	7.9 Percent change Standard Deviation 30.30	5.2 Percent change Standard Deviation 23.43	3.3 Percent change Standard Deviation 27.68	2.1 Percent change Standard Deviation 18.62
Percent Change From Baseline in Fasting Levels of Total Cholesterol (TC), Triglyceride (TG), Glucose, Low Density Lipoprotein Cholesterol (LDLc), Apolipoprotein A2 (ApoAII), Apolipoprotein B (ApoB) Over 8 Weeks of Administration With GSK256073 or Placebo ApoB, Week 2	-8.1 Percent change Standard Deviation 12.59	-9.8 Percent change Standard Deviation 9.42	-2.2 Percent change Standard Deviation 24.05	-2.6 Percent change Standard Deviation 7.58
Percent Change From Baseline in Fasting Levels of Total Cholesterol (TC), Triglyceride (TG), Glucose, Low Density Lipoprotein Cholesterol (LDLc), Apolipoprotein A2 (ApoAII), Apolipoprotein B (ApoB) Over 8 Weeks of Administration With GSK256073 or Placebo ApoB, Week 4	-3.4 Percent change Standard Deviation 8.85	-6.1 Percent change Standard Deviation 7.45	2.0 Percent change Standard Deviation 22.30	-0.8 Percent change Standard Deviation 11.16
Percent Change From Baseline in Fasting Levels of Total Cholesterol (TC), Triglyceride (TG), Glucose, Low Density Lipoprotein Cholesterol (LDLc), Apolipoprotein A2 (ApoAII), Apolipoprotein B (ApoB) Over 8 Weeks of Administration With GSK256073 or Placebo ApoB, Week 6	-3.8 Percent change Standard Deviation 11.51	-6.5 Percent change Standard Deviation 11.14	5.9 Percent change Standard Deviation 26.74	-1.8 Percent change Standard Deviation 8.86
Percent Change From Baseline in Fasting Levels of Total Cholesterol (TC), Triglyceride (TG), Glucose, Low Density Lipoprotein Cholesterol (LDLc), Apolipoprotein A2 (ApoAII), Apolipoprotein B (ApoB) Over 8 Weeks of Administration With GSK256073 or Placebo ApoB, Week 8	-2.8 Percent change Standard Deviation 12.82	-5.1 Percent change Standard Deviation 12.14	6.5 Percent change Standard Deviation 22.21	-0.8 Percent change Standard Deviation 8.37
Percent Change From Baseline in Fasting Levels of Total Cholesterol (TC), Triglyceride (TG), Glucose, Low Density Lipoprotein Cholesterol (LDLc), Apolipoprotein A2 (ApoAII), Apolipoprotein B (ApoB) Over 8 Weeks of Administration With GSK256073 or Placebo Glucose, Week 2	0.1 Percent change Standard Deviation 8.74	7.0 Percent change Standard Deviation 20.03	0.6 Percent change Standard Deviation 13.64	2.8 Percent change Standard Deviation 6.93
Percent Change From Baseline in Fasting Levels of Total Cholesterol (TC), Triglyceride (TG), Glucose, Low Density Lipoprotein Cholesterol (LDLc), Apolipoprotein A2 (ApoAII), Apolipoprotein B (ApoB) Over 8 Weeks of Administration With GSK256073 or Placebo Glucose, Week 4	-0.3 Percent change Standard Deviation 4.69	1.2 Percent change Standard Deviation 10.50	-2.2 Percent change Standard Deviation 16.13	0.9 Percent change Standard Deviation 8.68
Percent Change From Baseline in Fasting Levels of Total Cholesterol (TC), Triglyceride (TG), Glucose, Low Density Lipoprotein Cholesterol (LDLc), Apolipoprotein A2 (ApoAII), Apolipoprotein B (ApoB) Over 8 Weeks of Administration With GSK256073 or Placebo Glucose, Week 6	0.7 Percent change Standard Deviation 5.75	2.3 Percent change Standard Deviation 13.37	-2.6 Percent change Standard Deviation 13.49	1.0 Percent change Standard Deviation 9.79
Percent Change From Baseline in Fasting Levels of Total Cholesterol (TC), Triglyceride (TG), Glucose, Low Density Lipoprotein Cholesterol (LDLc), Apolipoprotein A2 (ApoAII), Apolipoprotein B (ApoB) Over 8 Weeks of Administration With GSK256073 or Placebo Glucose, Week 8	-1.0 Percent change Standard Deviation 10.19	2.6 Percent change Standard Deviation 9.40	-6.1 Percent change Standard Deviation 14.98	-0.0 Percent change Standard Deviation 9.85
Percent Change From Baseline in Fasting Levels of Total Cholesterol (TC), Triglyceride (TG), Glucose, Low Density Lipoprotein Cholesterol (LDLc), Apolipoprotein A2 (ApoAII), Apolipoprotein B (ApoB) Over 8 Weeks of Administration With GSK256073 or Placebo LDLc, Week 2	-2.7 Percent change Standard Deviation 10.77	-10.0 Percent change Standard Deviation 12.24	2.1 Percent change Standard Deviation 42.50	-2.9 Percent change Standard Deviation 12.08
Percent Change From Baseline in Fasting Levels of Total Cholesterol (TC), Triglyceride (TG), Glucose, Low Density Lipoprotein Cholesterol (LDLc), Apolipoprotein A2 (ApoAII), Apolipoprotein B (ApoB) Over 8 Weeks of Administration With GSK256073 or Placebo LDLc, Week 4	-6.7 Percent change Standard Deviation 6.19	-7.4 Percent change Standard Deviation 12.11	7.6 Percent change Standard Deviation 50.51	-3.0 Percent change Standard Deviation 12.28
Percent Change From Baseline in Fasting Levels of Total Cholesterol (TC), Triglyceride (TG), Glucose, Low Density Lipoprotein Cholesterol (LDLc), Apolipoprotein A2 (ApoAII), Apolipoprotein B (ApoB) Over 8 Weeks of Administration With GSK256073 or Placebo LDLc, Week 6	-4.3 Percent change Standard Deviation 12.54	-7.9 Percent change Standard Deviation 11.85	7.7 Percent change Standard Deviation 50.11	0.6 Percent change Standard Deviation 13.09
Percent Change From Baseline in Fasting Levels of Total Cholesterol (TC), Triglyceride (TG), Glucose, Low Density Lipoprotein Cholesterol (LDLc), Apolipoprotein A2 (ApoAII), Apolipoprotein B (ApoB) Over 8 Weeks of Administration With GSK256073 or Placebo LDLc, Week 8	-1.8 Percent change Standard Deviation 12.25	-6.5 Percent change Standard Deviation 12.01	8.4 Percent change Standard Deviation 50.73	-3.0 Percent change Standard Deviation 7.75
Percent Change From Baseline in Fasting Levels of Total Cholesterol (TC), Triglyceride (TG), Glucose, Low Density Lipoprotein Cholesterol (LDLc), Apolipoprotein A2 (ApoAII), Apolipoprotein B (ApoB) Over 8 Weeks of Administration With GSK256073 or Placebo TC, Week 2	-4.0 Percent change Standard Deviation 7.10	-9.3 Percent change Standard Deviation 8.28	-3.3 Percent change Standard Deviation 14.22	-2.4 Percent change Standard Deviation 6.58
Percent Change From Baseline in Fasting Levels of Total Cholesterol (TC), Triglyceride (TG), Glucose, Low Density Lipoprotein Cholesterol (LDLc), Apolipoprotein A2 (ApoAII), Apolipoprotein B (ApoB) Over 8 Weeks of Administration With GSK256073 or Placebo TC, Week 4	-4.8 Percent change Standard Deviation 5.28	-5.9 Percent change Standard Deviation 7.36	-0.8 Percent change Standard Deviation 12.57	-2.5 Percent change Standard Deviation 9.07
Percent Change From Baseline in Fasting Levels of Total Cholesterol (TC), Triglyceride (TG), Glucose, Low Density Lipoprotein Cholesterol (LDLc), Apolipoprotein A2 (ApoAII), Apolipoprotein B (ApoB) Over 8 Weeks of Administration With GSK256073 or Placebo TC, Week 6	-2.9 Percent change Standard Deviation 8.63	-6.2 Percent change Standard Deviation 9.10	-0.5 Percent change Standard Deviation 13.54	-1.3 Percent change Standard Deviation 7.81
Percent Change From Baseline in Fasting Levels of Total Cholesterol (TC), Triglyceride (TG), Glucose, Low Density Lipoprotein Cholesterol (LDLc), Apolipoprotein A2 (ApoAII), Apolipoprotein B (ApoB) Over 8 Weeks of Administration With GSK256073 or Placebo TC, Week 8	-0.5 Percent change Standard Deviation 9.00	-5.7 Percent change Standard Deviation 8.96	1.3 Percent change Standard Deviation 12.09	-2.1 Percent change Standard Deviation 5.49
Percent Change From Baseline in Fasting Levels of Total Cholesterol (TC), Triglyceride (TG), Glucose, Low Density Lipoprotein Cholesterol (LDLc), Apolipoprotein A2 (ApoAII), Apolipoprotein B (ApoB) Over 8 Weeks of Administration With GSK256073 or Placebo TG, Week 2	2.2 Percent change Standard Deviation 32.06	16.9 Percent change Standard Deviation 108.85	8.9 Percent change Standard Deviation 48.90	6.6 Percent change Standard Deviation 30.75

SECONDARY outcome

Timeframe: Baseline (Week 0) up to Week 8

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

Blood samples for analysis of insulin was collected at Baseline (Week 0) and Week 2, 4, 6 and 8. Baseline was defined at Week 0. Change from Baseline was calculated by subtracting the post-Baseline value from the Baseline value. Percent change from Baseline was calculated by multiplying change from Baseline value with 100.

Outcome measures

Outcome measures
Measure	GSK256073 5 mg n=19 Participants Eligible participants received GSK256073 5 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 50 mg n=20 Participants Eligible participants received GSK256073 50 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 150 mg n=20 Participants Eligible participants received GSK256073 150 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	Placebo n=21 Participants Eligible participants received placebo matching GSK256073 oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.
Percent Change From Baseline in Insulin Over Eight Weeks of Administration With GSK256073 or Placebo Week 8	2.8 Percent change Standard Deviation 20.31	18.3 Percent change Standard Deviation 47.56	13.7 Percent change Standard Deviation 41.44	-0.2 Percent change Standard Deviation 29.89
Percent Change From Baseline in Insulin Over Eight Weeks of Administration With GSK256073 or Placebo Week 2	23.1 Percent change Standard Deviation 82.20	21.2 Percent change Standard Deviation 72.27	25.3 Percent change Standard Deviation 92.41	-2.8 Percent change Standard Deviation 26.29
Percent Change From Baseline in Insulin Over Eight Weeks of Administration With GSK256073 or Placebo Week 4	9.1 Percent change Standard Deviation 22.14	16.3 Percent change Standard Deviation 73.97	13.2 Percent change Standard Deviation 50.01	-3.8 Percent change Standard Deviation 22.33
Percent Change From Baseline in Insulin Over Eight Weeks of Administration With GSK256073 or Placebo Week 6	16.6 Percent change Standard Deviation 43.40	17.8 Percent change Standard Deviation 35.16	4.2 Percent change Standard Deviation 44.83	-3.4 Percent change Standard Deviation 30.48

SECONDARY outcome

Timeframe: Baseline (Week 0) up to Week 8

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

Blood samples for analysis of Lp\[a\] was collected at Baseline (Week 0) and Week 2, 4, 6 and 8. Baseline was defined at Week 0. Change from Baseline was calculated by subtracting the post-Baseline value from the Baseline value. Percent change from Baseline was calculated by multiplying change from Baseline value with 100.

Outcome measures

Outcome measures
Measure	GSK256073 5 mg n=19 Participants Eligible participants received GSK256073 5 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 50 mg n=20 Participants Eligible participants received GSK256073 50 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 150 mg n=20 Participants Eligible participants received GSK256073 150 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	Placebo n=21 Participants Eligible participants received placebo matching GSK256073 oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.
Percent Change From Baseline in Lipoprotein (a) (Lp[a]) Over Eight Weeks of Administration With GSK256073 or Placebo Week 2	1.8 Percent change Standard Deviation 13.10	-10.3 Percent change Standard Deviation 13.52	4.5 Percent change Standard Deviation 26.28	-4.6 Percent change Standard Deviation 14.91
Percent Change From Baseline in Lipoprotein (a) (Lp[a]) Over Eight Weeks of Administration With GSK256073 or Placebo Week 4	-6.6 Percent change Standard Deviation 20.62	-11.3 Percent change Standard Deviation 11.94	1.6 Percent change Standard Deviation 19.33	-1.7 Percent change Standard Deviation 15.78
Percent Change From Baseline in Lipoprotein (a) (Lp[a]) Over Eight Weeks of Administration With GSK256073 or Placebo Week 8	4.0 Percent change Standard Deviation 13.56	-15.8 Percent change Standard Deviation 15.71	6.4 Percent change Standard Deviation 18.87	-5.6 Percent change Standard Deviation 31.64
Percent Change From Baseline in Lipoprotein (a) (Lp[a]) Over Eight Weeks of Administration With GSK256073 or Placebo Week 6	2.7 Percent change Standard Deviation 18.04	-7.3 Percent change Standard Deviation 16.50	6.5 Percent change Standard Deviation 32.24	-1.7 Percent change Standard Deviation 13.73

SECONDARY outcome

Timeframe: Baseline (Week 0) up to Week 8

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

Blood samples for analysis of NEFA was collected at Baseline (Week 0) and Week 2, 4, 6 and 8. Baseline was defined at Week 0. Change from Baseline was calculated by subtracting the post-Baseline value from the Baseline value. Percent change from Baseline was calculated by multiplying change from Baseline value with 100.

Outcome measures

Outcome measures
Measure	GSK256073 5 mg n=19 Participants Eligible participants received GSK256073 5 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 50 mg n=20 Participants Eligible participants received GSK256073 50 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 150 mg n=20 Participants Eligible participants received GSK256073 150 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	Placebo n=21 Participants Eligible participants received placebo matching GSK256073 oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.
Percent Change From Baseline in Non-esterified Fatty Acids (NEFA) Over Eight Weeks of Administration With GSK256073 or Placebo Week 2	32.1 Percent change Standard Deviation 68.56	16.8 Percent change Standard Deviation 53.84	29.1 Percent change Standard Deviation 75.28	24.4 Percent change Standard Deviation 44.56
Percent Change From Baseline in Non-esterified Fatty Acids (NEFA) Over Eight Weeks of Administration With GSK256073 or Placebo Week 4	38.8 Percent change Standard Deviation 70.88	37.4 Percent change Standard Deviation 91.98	26.2 Percent change Standard Deviation 80.52	7.0 Percent change Standard Deviation 31.02
Percent Change From Baseline in Non-esterified Fatty Acids (NEFA) Over Eight Weeks of Administration With GSK256073 or Placebo Week 6	47.8 Percent change Standard Deviation 89.62	29.1 Percent change Standard Deviation 73.47	8.0 Percent change Standard Deviation 61.33	-1.1 Percent change Standard Deviation 28.66
Percent Change From Baseline in Non-esterified Fatty Acids (NEFA) Over Eight Weeks of Administration With GSK256073 or Placebo Week 8	56.6 Percent change Standard Deviation 112.49	59.4 Percent change Standard Deviation 134.96	19.3 Percent change Standard Deviation 60.35	10.4 Percent change Standard Deviation 34.75

SECONDARY outcome

Timeframe: 0-2 hours after dosing (pre-dose plus 3 samples spaced at least 30 minutes apart), 2 to 4.5 hours after dose (3 samples spaced at least 30 minutes apart) and 6-12 hours post dose (3 samples spaced at least 30 minutes apart) on Week 2, 4, 6 and 8

Population: PK Population was defined as all participants in the PK concentration population for whom PK parameters had been derived.

All participants treated with GSK256073 or placebo participated in PK sampling. Blood samples for PK analysis of GSK256073 to determine Cmax was collected at Week 2, 4, 6 and 8. For samples obtained during time windows, every attempt was made to collect three samples during each time window: pre-dose to 2 hours after dosing, 2 hours to 4.5 hours after dose, and 6 hours to 12 hours after dose. During each window, 3 samples spaced at least 30 minutes apart were collected (i.e., avoid collection from all participants at the same time within a window or only at the extremes of a time window). The first occurrence of the Cmax was determined directly from the raw concentration-time data.

Outcome measures

Outcome measures
Measure	GSK256073 5 mg n=15 Participants Eligible participants received GSK256073 5 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 50 mg n=15 Participants Eligible participants received GSK256073 50 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 150 mg n=17 Participants Eligible participants received GSK256073 150 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	Placebo Eligible participants received placebo matching GSK256073 oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.
Plasma PK- Maximum Observed Concentration (Cmax)	923.709 Nanograms per mililiter (ng/mL) Geometric Coefficient of Variation 128.18	7223.709 Nanograms per mililiter (ng/mL) Geometric Coefficient of Variation 35.09	22961.25 Nanograms per mililiter (ng/mL) Geometric Coefficient of Variation 62.36	—

SECONDARY outcome

Population: PK Population.

All participants treated with GSK256073 or placebo participated in PK sampling. Blood samples for PK analysis of GSK256073 to determine Tmax was collected at Week 2, 4, 6 and 8. For samples obtained during time windows, every attempt was made to collect three samples during each time window: pre-dose to 2 hours after dosing, 2 hours to 4.5 hours after dose, and 6 hours to 12 hours after dose. During each window, 3 samples spaced at least 30 minutes apart were collected (i.e., avoid collection from all participants at the same time within a window or only at the extremes of a time window). The time at which Cmax was observed was determined directly from the raw concentration-time data.

Outcome measures

Outcome measures
Measure	GSK256073 5 mg n=15 Participants Eligible participants received GSK256073 5 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 50 mg n=15 Participants Eligible participants received GSK256073 50 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 150 mg n=17 Participants Eligible participants received GSK256073 150 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	Placebo Eligible participants received placebo matching GSK256073 oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.
Plasma PK- Time of Occurrence of Cmax (Tmax)	2.417 Hours Interval 0.5 to 7.73	1.350 Hours Interval 0.63 to 9.0	2.500 Hours Interval 0.5 to 25.98	—

SECONDARY outcome

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

All participants treated with GSK256073 or placebo participated in PK sampling. Blood samples for PK analysis of GSK256073 to determine AUC(0-t) was collected at Week 2, 4, 6 and 8. For samples obtained during time windows, every attempt was made to collect three samples during each time window: pre-dose to 2 hours after dosing, 2 hours to 4.5 hours after dose, and 6 hours to 12 hours after dose. During each window, 3 samples spaced at least 30 minutes apart were collected (i.e., avoid collection from all participants at the same time within a window or only at the extremes of a time window). The AUC 0-t was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.

Outcome measures

Outcome measures
Measure	GSK256073 5 mg n=15 Participants Eligible participants received GSK256073 5 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 50 mg n=15 Participants Eligible participants received GSK256073 50 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	GSK256073 150 mg n=16 Participants Eligible participants received GSK256073 150 mg oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.	Placebo Eligible participants received placebo matching GSK256073 oral tablet once daily for 60 days. Participants were provided study medication at the Baseline/randomization Visit. Study medication was self administered each morning (in a fed state) for 60 consecutive days during the out-patient visit. Participant were given a new supply of study medication approximately every 2 weeks at the out-patient visits.
Plasma PK- AUC(0-t)	8352.281 Hour nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 99.96	75587.96 Hour nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 71.88	340551.4 Hour nanogram per milliliter (h*ng/mL) Geometric Coefficient of Variation 60.67	—

Adverse Events

GSK256073 5 mg

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

GSK256073 50 mg

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

GSK256073 150 mg

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

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