Trial Outcomes & Findings for Study to Compare the Safety and Anti-HIV Effect of GSK1265744 Versus Placebo in HIV-1 Infected Adults (ITZ112929) (NCT NCT00920426)

NCT ID: NCT00920426

Last Updated: 2017-12-06

Results Overview

Blood samples for assessment of clinical chemistry parameters of chloride, carbon dioxide content/bicarbonate, magnesium, sodium and potassium was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 9 participants
• Primary outcome timeframe: Baseline (Day 1) and Day 3, 7, 10
• Results posted on: 2017-12-06

Participant Flow

This study was conducted at 4 centers in the United States from 09 June 2009 to 13 August 2009.

A total of 9 participants were randomized in the current study to receive 5 milligrams (mg) of GSK1265744 or Placebo. A total of 8 participants were previously randomized in study ITZ111451 part C HIV cohort, NCT00659191 to receive 30 mg of GSK1265744 once daily.

Participant milestones

Measure	GSK1265744 30 mg GSK1265744 30 mg once daily was previously studied in study ITZ111451 part C HIV cohort, NCT00659191. Eligible participants received repeat doses of GSK1265744 30 mg (6x5 mg) oral tablets once daily for 10 days.	GSK1265744 5 mg Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
ITZ111451 STARTED	8	0	0	0
ITZ111451 COMPLETED	7	0	0	0
ITZ111451 NOT COMPLETED	1	0	0	0
ITZ112929: Randomized Regimen STARTED	0	7	2	0
ITZ112929: Randomized Regimen COMPLETED	0	7	2	0
ITZ112929: Randomized Regimen NOT COMPLETED	0	0	0	0
ITZ112929: Optimized Therapy (OT) STARTED	0	0	0	8
ITZ112929: Optimized Therapy (OT) COMPLETED	0	0	0	8
ITZ112929: Optimized Therapy (OT) NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Measure	GSK1265744 30 mg GSK1265744 30 mg once daily was previously studied in study ITZ111451 part C HIV cohort, NCT00659191. Eligible participants received repeat doses of GSK1265744 30 mg (6x5 mg) oral tablets once daily for 10 days.	GSK1265744 5 mg Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
ITZ111451 Adverse Event	1	0	0	0

Baseline Characteristics

Study to Compare the Safety and Anti-HIV Effect of GSK1265744 Versus Placebo in HIV-1 Infected Adults (ITZ112929)

Baseline characteristics by cohort

Measure	GSK1265744 30 mg n=8 Participants GSK1265744 30 mg once daily was previously studied in study ITZ111451 part C HIV cohort, NCT00659191. Eligible participants received repeat doses of GSK1265744 30 mg (6x5 mg) oral tablets once daily for 10 days.	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo n=2 Participants Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Total n=17 Participants Total of all reporting groups
Age, Customized 27 to 51 Years	8 Participants n=5 Participants	7 Participants n=7 Participants	2 Participants n=5 Participants	17 Participants n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	5 Participants n=7 Participants	2 Participants n=5 Participants	15 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 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
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
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	5 Participants n=7 Participants	2 Participants n=5 Participants	15 Participants n=4 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
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

PRIMARY outcome

Timeframe: Baseline (Day 1) and Day 11

Population: Intent-to-treat (ITT) population comprised of all participants who met study criteria and randomized into study with documented evidence of having received at least 1 dose of randomized treatment and at least 1 post-baseline HIV-1 RNA measurement. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Plasma for quantitative HIV-1 RNA was collected on Day 1, 2, 3, 4, 7, 8, 9, 10 and 11. On Days 1, 10 and 11, two samples for HIV-1 RNA was collected between 5-20 minutes apart to reduce sample variability. An HIV-1 RNA PCR assay with a lower limit of detection (LLOD) of 50 copies/milliliter (mL) (ultrasensitive assay) was used for post-baseline assessments. An HIV-1 RNA PCR assay with a LLOD of 400 copies/mL (standard assay) was used for screening and Baseline assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo n=2 Participants Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Change From Baseline in Plasma Human Immunodeficiency Virus (HIV-1) Ribonucleic Acid (RNA) to Day 11	-2.169 log10 copies/mL Standard Deviation 0.2405	-0.092 log10 copies/mL Standard Deviation 0.1499	—

PRIMARY outcome

Timeframe: Day 1 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose)

Population: PK Summary Population included participants with evaluable PK profile of GSK1265744 on Day 10. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Blood samples for PK analysis of AUC(0-24) of GSK1265744 was collected on Day 1 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose). Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded. AUC was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
GSK1265744 Pharmacokinetic (PK) Parameters Following Dose Administration on Day 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Within a Participant Across All Treatments(AUC[0-24])	7.53 Hour*microgram per milliliter (hr*µg/mL) Geometric Coefficient of Variation 23	—	—

PRIMARY outcome

Timeframe: Day 1 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose)

Population: PK summary population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Blood samples for PK analysis of C24 of GSK1265744 was collected on Day 1 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose). Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
GSK1265744 PK Parameters Following Dose Administration on Day 1: Concentration at 24 Hours Post Dose (C24)	0.23 Micrograms per milliliter (µg/mL) Geometric Coefficient of Variation 28	—	—

PRIMARY outcome

Timeframe: Day 10 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose)

Population: PK summary population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Blood samples for PK analysis of C24 of GSK1265744 was collected on Day 10 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose). Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded. AUC was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
GSK1265744 PK Parameters Following Dose Administration on Day 10: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau])	17.74 hr*µg/mL Geometric Coefficient of Variation 31	—	—

PRIMARY outcome

Timeframe: Day 10 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose)

Population: PK Summary Population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Blood samples for PK analysis of C0, Ctau and Cmin of GSK1265744 was collected on Day 10 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose). Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
GSK1265744 PK Parameters Following Dose Administration on Day 10: Predose Concentration (C0), Concentration at End of Dosing Interval (Ctau), Minimum Observed Concentration During One Dosing Interval (Cmin) C0	0.54 µg/mL Geometric Coefficient of Variation 36	—	—
GSK1265744 PK Parameters Following Dose Administration on Day 10: Predose Concentration (C0), Concentration at End of Dosing Interval (Ctau), Minimum Observed Concentration During One Dosing Interval (Cmin) Ctau	0.57 µg/mL Geometric Coefficient of Variation 33	—	—
GSK1265744 PK Parameters Following Dose Administration on Day 10: Predose Concentration (C0), Concentration at End of Dosing Interval (Ctau), Minimum Observed Concentration During One Dosing Interval (Cmin) Cmin	0.53 µg/mL Geometric Coefficient of Variation 35	—	—

PRIMARY outcome

Timeframe: Pre-dose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose on Days 1 and 10

Population: PK Summary Population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Blood samples for PK analysis of Cmax of GSK1265744 was collected at pre-dose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose on Days 1 and 10. Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
GSK1265744 PK Parameters Following Dose Administration on Day 1 and Day 10: Maximum Observed Concentration (Cmax) Day 1	0.52 µg/mL Geometric Coefficient of Variation 20	—	—
GSK1265744 PK Parameters Following Dose Administration on Day 1 and Day 10: Maximum Observed Concentration (Cmax) Day 10	1.02 µg/mL Geometric Coefficient of Variation 25	—	—

PRIMARY outcome

Timeframe: Pre-dose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose on Days 1 and 10

Population: PK Summary Population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Blood samples for PK analysis of tmax of GSK1265744 was collected at pre-dose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose on Days 1 and 10. Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
GSK1265744 PK Parameters Following Dose Administration on Day 1 and Day 10: Time to Cmax (Tmax) Day 1	2.00 Hour Interval 1.0 to 4.08	—	—
GSK1265744 PK Parameters Following Dose Administration on Day 1 and Day 10: Time to Cmax (Tmax) Day 10	2.00 Hour Interval 1.5 to 4.08	—	—

PRIMARY outcome

Timeframe: Day 1 and Day 10

Population: PK Summary Population. Data for this outcome measure was not collected. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

PK sampling was planned to be collected up to 24 hours only on Day 1 and Day 10. The data for this outcome measure was however not collected.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 10 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose)

Population: PK Summary Population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Blood samples for PK analysis of CL/F of GSK1265744 was collected on Day 10 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose). Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
GSK1265744 PK Parameters Following Last Repeat Administration on Day 10: Apparent Clearance Following Oral Dosing (CL/F)	0.28 Liter per hour (L/hr) Geometric Coefficient of Variation 31	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 11

Population: Safety population was defined as all participants who were randomized into the study with documented evidence of having received at least 1 dose of randomized treatment. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

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 AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. 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 is associated with liver injury and impaired liver function.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo n=2 Participants Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy n=8 Participants Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Number of Participants With Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AEs	0 Participants	2 Participants	3 Participants
Number of Participants With Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) Any SAEs	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) and Day 3, 7, 10

Population: Safety population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Blood samples for assessment of hematology parameters of basophils, eosinophils, lymphocytes, monocytes, total neutrophils (ANC- absolute neutrophil count) and white blood cell count was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo n=2 Participants Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count Lymphocytes, Day 3	0.197 Thousand cells per microliter Standard Deviation 0.2870	-0.500 Thousand cells per microliter Standard Deviation 0.3111	—
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count Eosinophils, Day 7	-0.039 Thousand cells per microliter Standard Deviation 0.0498	0.325 Thousand cells per microliter Standard Deviation 0.5869	—
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count Eosinophils, Day 10	-0.009 Thousand cells per microliter Standard Deviation 0.0628	-0.055 Thousand cells per microliter Standard Deviation 0.1485	—
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count Lymphocytes, Day 7	0.190 Thousand cells per microliter Standard Deviation 0.2514	-0.525 Thousand cells per microliter Standard Deviation 0.1485	—
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count Lymphocytes, Day 10	0.229 Thousand cells per microliter Standard Deviation 0.2738	-0.720 Thousand cells per microliter Standard Deviation 0.5515	—
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count Monocytes, Day 3	-0.030 Thousand cells per microliter Standard Deviation 0.0876	0.170 Thousand cells per microliter Standard Deviation 0.2121	—
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count Monocytes, Day 7	-0.039 Thousand cells per microliter Standard Deviation 0.1126	0.035 Thousand cells per microliter Standard Deviation 0.1626	—
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count Monocytes, Day 10	0.056 Thousand cells per microliter Standard Deviation 0.0774	-0.005 Thousand cells per microliter Standard Deviation 0.2192	—
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count Total Neutrophils, Day 3	0.181 Thousand cells per microliter Standard Deviation 0.6097	-0.080 Thousand cells per microliter Standard Deviation 0.1273	—
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count Total Neutrophils, Day 7	-0.003 Thousand cells per microliter Standard Deviation 0.6304	-0.155 Thousand cells per microliter Standard Deviation 0.2192	—
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count Total Neutrophils, Day 10	0.831 Thousand cells per microliter Standard Deviation 1.6043	0.405 Thousand cells per microliter Standard Deviation 1.1384	—
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count White blood cell count, Day 3	0.34 Thousand cells per microliter Standard Deviation 0.282	-0.15 Thousand cells per microliter Standard Deviation 1.061	—
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count White blood cell count, Day 7	0.11 Thousand cells per microliter Standard Deviation 0.782	-0.30 Thousand cells per microliter Standard Deviation 1.131	—
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count White blood cell count, Day 10	1.11 Thousand cells per microliter Standard Deviation 1.508	-0.35 Thousand cells per microliter Standard Deviation 1.626	—
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count Basophils, Day 10	0.009 Thousand cells per microliter Standard Deviation 0.0146	0.020 Thousand cells per microliter Standard Deviation 0.0000	—
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count Basophils, Day 3	0.017 Thousand cells per microliter Standard Deviation 0.0287	0.005 Thousand cells per microliter Standard Deviation 0.0071	—
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count Basophils, Day 7	0.007 Thousand cells per microliter Standard Deviation 0.0125	0.015 Thousand cells per microliter Standard Deviation 0.0071	—
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count Eosinophils, Day 3	-0.024 Thousand cells per microliter Standard Deviation 0.0408	0.250 Thousand cells per microliter Standard Deviation 0.4101	—

PRIMARY outcome

Timeframe: Baseline (Day 1) and Day 3, 7, 10

Population: Safety population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Blood samples for assessment of hematology parameter of hemoglobin was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo n=2 Participants Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Change From Baseline in Hematology Parameters: Hemoglobin Day 3	0.13 Grams per deciliter Standard Deviation 0.637	-0.30 Grams per deciliter Standard Deviation 0.424	—
Change From Baseline in Hematology Parameters: Hemoglobin Day 7	0.06 Grams per deciliter Standard Deviation 0.519	0.00 Grams per deciliter Standard Deviation 0.424	—
Change From Baseline in Hematology Parameters: Hemoglobin Day 10	-0.17 Grams per deciliter Standard Deviation 0.446	-0.15 Grams per deciliter Standard Deviation 0.354	—

PRIMARY outcome

Timeframe: Baseline (Day 1) and Day 3, 7, 10

Population: Safety population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Blood samples for assessment of hematology parameter of mean corpuscle hemoglobin was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo n=2 Participants Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Change From Baseline in Hematology Parameters: Mean Corpuscle Hemoglobin Day 3	-0.03 Picogram Standard Deviation 0.198	0.25 Picogram Standard Deviation 0.495	—
Change From Baseline in Hematology Parameters: Mean Corpuscle Hemoglobin Day 7	0.37 Picogram Standard Deviation 0.411	0.30 Picogram Standard Deviation 0.141	—
Change From Baseline in Hematology Parameters: Mean Corpuscle Hemoglobin Day 10	0.00 Picogram Standard Deviation 0.306	0.40 Picogram Standard Deviation 0.424	—

PRIMARY outcome

Timeframe: Baseline (Day 1) and Day 3, 7, 10

Population: Safety Population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Blood samples for assessment of hematology parameter of mean corpuscle volume was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo n=2 Participants Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Change From Baseline in Hematology Parameters: Mean Corpuscle Volume Day 7	1.0 Femtoliter Standard Deviation 1.63	-0.5 Femtoliter Standard Deviation 0.71	—
Change From Baseline in Hematology Parameters: Mean Corpuscle Volume Day 10	1.7 Femtoliter Standard Deviation 1.11	0.0 Femtoliter Standard Deviation 1.41	—
Change From Baseline in Hematology Parameters: Mean Corpuscle Volume Day 3	1.0 Femtoliter Standard Deviation 1.15	0.5 Femtoliter Standard Deviation 0.71	—

PRIMARY outcome

Timeframe: Baseline (Day 1) and Day 3, 7, 10

Population: Safety population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Blood samples for assessment of hematology parameter of platelet count was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo n=2 Participants Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Change From Baseline in Hematology Parameters: Platelet Count Day 3	10428.6 Cells per cubic millimeter Standard Deviation 8847.92	5000.0 Cells per cubic millimeter Standard Deviation 21213.20	—
Change From Baseline in Hematology Parameters: Platelet Count Day 7	15142.9 Cells per cubic millimeter Standard Deviation 29299.76	2500.0 Cells per cubic millimeter Standard Deviation 2121.32	—
Change From Baseline in Hematology Parameters: Platelet Count Day 10	8000.0 Cells per cubic millimeter Standard Deviation 23860.71	9500.0 Cells per cubic millimeter Standard Deviation 37476.66	—

PRIMARY outcome

Timeframe: Baseline (Day 1) and Day 3, 7, 10

Population: Safety Population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Blood samples for assessment of hematology parameter of red blood cell count was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo n=2 Participants Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Change From Baseline in Hematology Parameters: Red Blood Cell Count Day 3	0.03 Million cells per microliter Standard Deviation 0.221	-0.15 Million cells per microliter Standard Deviation 0.071	—
Change From Baseline in Hematology Parameters: Red Blood Cell Count Day 7	-0.06 Million cells per microliter Standard Deviation 0.151	-0.05 Million cells per microliter Standard Deviation 0.071	—
Change From Baseline in Hematology Parameters: Red Blood Cell Count Day 10	-0.09 Million cells per microliter Standard Deviation 0.135	-0.10 Million cells per microliter Standard Deviation 0.141	—

PRIMARY outcome

Timeframe: Baseline (Day 1) and Day 3, 7, 10

Population: Safety Population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Blood samples for assessment of hematology parameter of reticulocytes was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo n=2 Participants Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Change From Baseline in Hematology Parameters: Reticulocytes Day 3	5.51 Giga cells per liter Standard Deviation 9.971	9.45 Giga cells per liter Standard Deviation 1.768	—
Change From Baseline in Hematology Parameters: Reticulocytes Day 7	13.79 Giga cells per liter Standard Deviation 27.361	-6.50 Giga cells per liter Standard Deviation 0.849	—
Change From Baseline in Hematology Parameters: Reticulocytes Day 10	13.79 Giga cells per liter Standard Deviation 16.419	21.30 Giga cells per liter Standard Deviation 35.497	—

PRIMARY outcome

Timeframe: Baseline (Day 1) and Day 3, 7, 10

Population: Safety Population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Blood samples for assessment of clinical chemistry parameters of albumin and total protein was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo n=2 Participants Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Change From Baseline in Clinical Chemistry Data: Albumin, Total Protein Albumin, Day 3	0.16 Grams per deciliter Standard Deviation 0.162	0.00 Grams per deciliter Standard Deviation 0.000	—
Change From Baseline in Clinical Chemistry Data: Albumin, Total Protein Albumin, Day 7	0.08 Grams per deciliter Standard Deviation 0.117	0.05 Grams per deciliter Standard Deviation 0.071	—
Change From Baseline in Clinical Chemistry Data: Albumin, Total Protein Albumin, Day 10	0.06 Grams per deciliter Standard Deviation 0.098	0.15 Grams per deciliter Standard Deviation 0.071	—
Change From Baseline in Clinical Chemistry Data: Albumin, Total Protein Total protein, Day 3	0.24 Grams per deciliter Standard Deviation 0.447	0.05 Grams per deciliter Standard Deviation 0.212	—
Change From Baseline in Clinical Chemistry Data: Albumin, Total Protein Total protein, Day 7	0.03 Grams per deciliter Standard Deviation 0.294	0.10 Grams per deciliter Standard Deviation 0.424	—
Change From Baseline in Clinical Chemistry Data: Albumin, Total Protein Total protein, Day 10	-0.10 Grams per deciliter Standard Deviation 0.342	0.10 Grams per deciliter Standard Deviation 0.000	—

PRIMARY outcome

Timeframe: Baseline (Day 1) and Day 3, 7, 10

Population: Safety Population. Only those participants available at the indicated time points were analyzed. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Blood samples for assessment of clinical chemistry parameters of alkaline phosphatase, alanine amino transferase, aspartate amino transferase, creatine kinase and lipase was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo n=2 Participants Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase Alkaline phosphatase, Day 3	1.6 Units per liter Standard Deviation 3.10	-3.5 Units per liter Standard Deviation 4.95	—
Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase Alkaline phosphatase, Day 7	0.5 Units per liter Standard Deviation 3.89	-5.0 Units per liter Standard Deviation 0.00	—
Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase Alkaline phosphatase, Day 10	-2.4 Units per liter Standard Deviation 6.55	-4.0 Units per liter Standard Deviation 2.83	—
Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase Alanine amino transferase, Day 3	2.9 Units per liter Standard Deviation 6.41	-4.0 Units per liter Standard Deviation 2.83	—
Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase Alanine amino transferase, Day 7	-0.2 Units per liter Standard Deviation 4.02	-1.5 Units per liter Standard Deviation 9.19	—
Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase Alanine amino transferase, Day 10	2.0 Units per liter Standard Deviation 4.12	-2.5 Units per liter Standard Deviation 7.78	—
Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase Aspartate amino transferase, Day 3	-1.0 Units per liter Standard Deviation 4.28	-2.0 Units per liter Standard Deviation 8.49	—
Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase Aspartate amino transferase, Day 7	-1.0 Units per liter Standard Deviation 3.52	-3.5 Units per liter Standard Deviation 7.78	—
Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase Aspartate amino transferase, Day 10	0.4 Units per liter Standard Deviation 5.32	-2.0 Units per liter Standard Deviation 5.66	—
Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase Creatine kinase, Day 3	-0.1 Units per liter Standard Deviation 11.42	-29.5 Units per liter Standard Deviation 10.61	—
Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase Creatine kinase, Day 7	27.7 Units per liter Standard Deviation 77.11	-48.0 Units per liter Standard Deviation 42.43	—
Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase Creatine kinase, Day 10	20.6 Units per liter Standard Deviation 42.97	-40.5 Units per liter Standard Deviation 43.13	—
Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase Lipase, Day 3	0.9 Units per liter Standard Deviation 8.91	4.0 Units per liter Standard Deviation 2.83	—
Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase Lipase, Day 7	-0.9 Units per liter Standard Deviation 17.22	-1.0 Units per liter Standard Deviation 8.49	—
Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase Lipase, Day 10	0.3 Units per liter Standard Deviation 14.42	-2.0 Units per liter Standard Deviation 2.83	—

PRIMARY outcome

Timeframe: Baseline (Day 1) and Day 3, 7, 10

Population: Safety population. Only those participants available at the indicated time points were analyzed. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Blood samples for assessment of clinical chemistry parameters of direct bilirubin, total bilirubin, calcium, cholesterol, creatinine, glucose, HDL cholesterol direct, LDL cholesterol calculation, triglycerides,Urea/BUN was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo n=2 Participants Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen LDL cholesterol calculation, Day 3	6.7 Milligrams per deciliter Standard Deviation 9.21	-7.0 Milligrams per deciliter Standard Deviation 12.73	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen Triglycerides, Day 7	258.3 Milligrams per deciliter Standard Deviation 636.46	-20.5 Milligrams per deciliter Standard Deviation 21.92	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen Triglycerides, Day 10	3.6 Milligrams per deciliter Standard Deviation 39.59	28.5 Milligrams per deciliter Standard Deviation 72.83	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen Urea/BUN, Day 3	1.4 Milligrams per deciliter Standard Deviation 2.15	-1.0 Milligrams per deciliter Standard Deviation 5.66	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen Urea/BUN, Day 7	1.3 Milligrams per deciliter Standard Deviation 3.27	-2.5 Milligrams per deciliter Standard Deviation 4.95	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen Urea/BUN, Day 10	0.7 Milligrams per deciliter Standard Deviation 2.81	-2.0 Milligrams per deciliter Standard Deviation 0.00	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen Direct bilirubin, Day 3	-0.04 Milligrams per deciliter Standard Deviation 0.113	-0.05 Milligrams per deciliter Standard Deviation 0.071	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen Direct bilirubin, Day 7	-0.10 Milligrams per deciliter Standard Deviation 0.126	-0.05 Milligrams per deciliter Standard Deviation 0.071	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen Direct bilirubin, Day 10	-0.06 Milligrams per deciliter Standard Deviation 0.053	0.00 Milligrams per deciliter Standard Deviation 0.000	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen Total bilirubin, Day 3	-0.06 Milligrams per deciliter Standard Deviation 0.207	-0.25 Milligrams per deciliter Standard Deviation 0.354	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen Total bilirubin, Day 7	-0.03 Milligrams per deciliter Standard Deviation 0.186	-0.40 Milligrams per deciliter Standard Deviation 0.566	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen Total bilirubin, Day 10	0.00 Milligrams per deciliter Standard Deviation 0.216	-0.10 Milligrams per deciliter Standard Deviation 0.141	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen Calcium, Day 3	0.13 Milligrams per deciliter Standard Deviation 0.198	0.00 Milligrams per deciliter Standard Deviation 0.141	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen Calcium, Day 7	0.17 Milligrams per deciliter Standard Deviation 0.207	0.05 Milligrams per deciliter Standard Deviation 0.495	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen Calcium, Day 10	-0.09 Milligrams per deciliter Standard Deviation 0.254	0.20 Milligrams per deciliter Standard Deviation 0.000	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen Cholesterol, Day 3	5.7 Milligrams per deciliter Standard Deviation 8.90	-7.5 Milligrams per deciliter Standard Deviation 9.19	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen Cholesterol, Day 7	16.2 Milligrams per deciliter Standard Deviation 32.60	0.0 Milligrams per deciliter Standard Deviation 1.41	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen Cholesterol, Day 10	4.0 Milligrams per deciliter Standard Deviation 13.17	1.0 Milligrams per deciliter Standard Deviation 2.83	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen Creatinine, Day 3	0.03 Milligrams per deciliter Standard Deviation 0.049	0.05 Milligrams per deciliter Standard Deviation 0.071	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen Creatinine, Day 7	0.05 Milligrams per deciliter Standard Deviation 0.105	0.05 Milligrams per deciliter Standard Deviation 0.071	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen Creatinine, Day 10	0.03 Milligrams per deciliter Standard Deviation 0.076	0.05 Milligrams per deciliter Standard Deviation 0.071	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen Glucose, Day 3	16.1 Milligrams per deciliter Standard Deviation 28.35	2.0 Milligrams per deciliter Standard Deviation 1.41	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen Glucose, Day 7	-16.5 Milligrams per deciliter Standard Deviation 45.62	4.5 Milligrams per deciliter Standard Deviation 3.54	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen Glucose, Day 10	0.1 Milligrams per deciliter Standard Deviation 5.81	-4.0 Milligrams per deciliter Standard Deviation 0.00	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen HDL cholesterol, direct, Day 3	-0.6 Milligrams per deciliter Standard Deviation 2.44	-1.5 Milligrams per deciliter Standard Deviation 2.12	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen HDL cholesterol, direct, Day 7	-0.2 Milligrams per deciliter Standard Deviation 9.62	0.5 Milligrams per deciliter Standard Deviation 0.71	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen HDL cholesterol, direct, Day 10	1.9 Milligrams per deciliter Standard Deviation 4.56	-2.0 Milligrams per deciliter Standard Deviation 1.41	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen LDL cholesterol calculation, Day 7	-0.2 Milligrams per deciliter Standard Deviation 9.93	3.5 Milligrams per deciliter Standard Deviation 6.36	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen LDL cholesterol calculation, Day 10	1.6 Milligrams per deciliter Standard Deviation 10.42	-2.5 Milligrams per deciliter Standard Deviation 16.26	—
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen Triglycerides, Day 3	-1.9 Milligrams per deciliter Standard Deviation 49.69	5.0 Milligrams per deciliter Standard Deviation 4.24	—

PRIMARY outcome

Timeframe: Baseline (Day 1) and Day 3, 7, 10

Population: Safety population. Only those participants available at the indicated time points were analyzed. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Blood samples for assessment of clinical chemistry parameters of chloride, carbon dioxide content/bicarbonate, magnesium, sodium and potassium was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo n=2 Participants Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium Chloride, Day 3	0.0 Milliequivalents per liter Standard Deviation 0.82	2.0 Milliequivalents per liter Standard Deviation 0.00	—
Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium Chloride, Day 7	-0.2 Milliequivalents per liter Standard Deviation 2.79	2.0 Milliequivalents per liter Standard Deviation 0.00	—
Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium Chloride, Day 10	-0.7 Milliequivalents per liter Standard Deviation 2.69	2.0 Milliequivalents per liter Standard Deviation 4.24	—
Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium Carbon dioxide content/Bicarbonate, Day 3	-0.9 Milliequivalents per liter Standard Deviation 2.41	-1.0 Milliequivalents per liter Standard Deviation 0.00	—
Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium Carbon dioxide content/Bicarbonate, Day 7	-1.3 Milliequivalents per liter Standard Deviation 1.63	-2.0 Milliequivalents per liter Standard Deviation 2.83	—
Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium Carbon dioxide content/Bicarbonate, Day 10	0.6 Milliequivalents per liter Standard Deviation 2.76	-2.0 Milliequivalents per liter Standard Deviation 2.83	—
Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium Potassium, Day 3	0.20 Milliequivalents per liter Standard Deviation 0.200	0.30 Milliequivalents per liter Standard Deviation 0.141	—
Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium Potassium, Day 7	0.00 Milliequivalents per liter Standard Deviation 0.245	0.20 Milliequivalents per liter Standard Deviation 0.283	—
Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium Potassium, Day 10	0.07 Milliequivalents per liter Standard Deviation 0.368	0.05 Milliequivalents per liter Standard Deviation 0.212	—
Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium Magnesium, Day 3	-0.04 Milliequivalents per liter Standard Deviation 0.098	0.10 Milliequivalents per liter Standard Deviation 0.000	—
Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium Magnesium, Day 7	-0.00 Milliequivalents per liter Standard Deviation 0.089	0.10 Milliequivalents per liter Standard Deviation 0.141	—
Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium Magnesium, Day 10	-0.04 Milliequivalents per liter Standard Deviation 0.098	0.00 Milliequivalents per liter Standard Deviation 0.141	—
Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium Sodium, Day 3	-0.4 Milliequivalents per liter Standard Deviation 1.62	0.5 Milliequivalents per liter Standard Deviation 0.71	—
Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium Sodium, Day 7	0.3 Milliequivalents per liter Standard Deviation 2.50	0.5 Milliequivalents per liter Standard Deviation 0.71	—
Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium Sodium, Day 10	-0.4 Milliequivalents per liter Standard Deviation 1.62	0.5 Milliequivalents per liter Standard Deviation 2.12	—

PRIMARY outcome

Timeframe: Day 1 to Day 10

Population: Safety Population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Samples for urinalysis assessment was collected on Day 1, Day 3 and Day 10. Urinalysis parameters included urine bilirubin, urine occult blood, urine glucose, urine ketones, urine nitrite, urine pH, urine protein, urine specific gravity and urine leukocyte esterase test for detecting white blood cell.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo n=2 Participants Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Number of Participants With Urinalysis Data Day 1, Urine Bilirubin, Negative	7 Participants	2 Participants	—
Number of Participants With Urinalysis Data Day 1, Urine Occult Blood, Negative	7 Participants	2 Participants	—
Number of Participants With Urinalysis Data Day 1, Urine Glucose, Negative	7 Participants	2 Participants	—
Number of Participants With Urinalysis Data Day 1, Urine Ketones, Negative	7 Participants	2 Participants	—
Number of Participants With Urinalysis Data Day 1, Urine Nitrite, Negative	6 Participants	2 Participants	—
Number of Participants With Urinalysis Data Day 1, Urine Nitrite, Positive	1 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 1, Urine pH, 5.5	2 Participants	1 Participants	—
Number of Participants With Urinalysis Data Day 1, Urine pH, 6	4 Participants	1 Participants	—
Number of Participants With Urinalysis Data Day 1, Urine pH, 6.5	1 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 1, Urine Protein, Negative	7 Participants	2 Participants	—
Number of Participants With Urinalysis Data Day 1, Urine Specific Gravity, 1.006	1 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 1, Urine Specific Gravity, 1.014	0 Participants	1 Participants	—
Number of Participants With Urinalysis Data Day 1, Urine Specific Gravity, 1.015	0 Participants	1 Participants	—
Number of Participants With Urinalysis Data Day 1, Urine Specific Gravity, 1.017	1 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 1, Urine Specific Gravity, 1.019	2 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 1, Urine Specific Gravity, 1.021	1 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 1, Urine Specific Gravity, 1.025	1 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 1, Urine Specific Gravity, 1.03	1 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 1, ULET for white blood cell, Negative	7 Participants	2 Participants	—
Number of Participants With Urinalysis Data Day 3, Urine Bilirubin, Negative	7 Participants	2 Participants	—
Number of Participants With Urinalysis Data Day 3, Urine Occult Blood, Negative	6 Participants	2 Participants	—
Number of Participants With Urinalysis Data Day 3, Urine Occult Blood, 1+	1 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 3, Urine Glucose, 3+	1 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 3, Urine Glucose, Negative	6 Participants	2 Participants	—
Number of Participants With Urinalysis Data Day 3, Urine Ketones, Negative	7 Participants	2 Participants	—
Number of Participants With Urinalysis Data Day 3, Urine Nitrite, Negative	6 Participants	2 Participants	—
Number of Participants With Urinalysis Data Day 3, Urine Nitrite, Positive	1 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 3, Urine pH, 5.5	4 Participants	1 Participants	—
Number of Participants With Urinalysis Data Day 3, Urine pH, 6	2 Participants	1 Participants	—
Number of Participants With Urinalysis Data Day 3, Urine pH, 6.5	1 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 3, Urine Protein, Negative	6 Participants	2 Participants	—
Number of Participants With Urinalysis Data Day 3, Urine Protein, Trace	1 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 3, Urine Specific Gravity, 1.016	1 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 3, Urine Specific Gravity, 1.017	1 Participants	1 Participants	—
Number of Participants With Urinalysis Data Day 3, Urine Specific Gravity, 1.018	0 Participants	1 Participants	—
Number of Participants With Urinalysis Data Day 3, Urine Specific Gravity, 1.021	2 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 3, Urine Specific Gravity, 1.022	1 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 3, Urine Specific Gravity, 1.027	1 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 3, Urine Specific Gravity, 1.03	1 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 3, ULET for white blood cell, 2+	1 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 3, ULET for white blood cell, Negative	6 Participants	2 Participants	—
Number of Participants With Urinalysis Data Day 10, Urine Bilirubin, Negative	7 Participants	2 Participants	—
Number of Participants With Urinalysis Data Day 10, Urine Occult Blood, 2+	1 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 10, Urine Occult Blood, Negative	6 Participants	2 Participants	—
Number of Participants With Urinalysis Data Day 10, Urine Glucose, Negative	7 Participants	2 Participants	—
Number of Participants With Urinalysis Data Day 10, Urine Ketones, Negative	7 Participants	2 Participants	—
Number of Participants With Urinalysis Data Day 10, Urine Nitrite, Negative	6 Participants	2 Participants	—
Number of Participants With Urinalysis Data Day 10, Urine Nitrite, Positive	1 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 10, Urine pH, 5.5	0 Participants	1 Participants	—
Number of Participants With Urinalysis Data Day 10, Urine pH, 6	4 Participants	1 Participants	—
Number of Participants With Urinalysis Data Day 10, Urine pH, 6.5	3 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 10, Urine Protein, Negative	5 Participants	2 Participants	—
Number of Participants With Urinalysis Data Day 10, Urine Protein, Trace	2 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 10, Urine Specific Gravity, 1.009	0 Participants	1 Participants	—
Number of Participants With Urinalysis Data Day 10, Urine Specific Gravity, 1.016	0 Participants	1 Participants	—
Number of Participants With Urinalysis Data Day 10, Urine Specific Gravity, 1.02	1 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 10, Urine Specific Gravity, 1.021	1 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 10, Urine Specific Gravity, 1.023	1 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 10, Urine Specific Gravity, 1.025	2 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 10, Urine Specific Gravity, 1.027	1 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 10, Urine Specific Gravity, 1.03	1 Participants	0 Participants	—
Number of Participants With Urinalysis Data Day 10, ULET for white blood cell, Negative	7 Participants	2 Participants	—

PRIMARY outcome

Timeframe: Baseline (Day 1, pre-dose) and Day 1 (2 hours post dose), 4, 7, 10

Population: Safety population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Systolic and diastolic blood pressure was measured at Baseline (Day 1 pre-dose), 2 hour post dose on Day 1, pre-dose on Day 4, 7, 10 and 2 hours post dose on Day 10. Baseline was defined at Day 1 pre-dose. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo n=2 Participants Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure Diastolic blood pressure, Day 10, Pre dose	-5.4 Millimeters of mercury (mmHg) Standard Deviation 13.85	8.5 Millimeters of mercury (mmHg) Standard Deviation 14.85	—
Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure Systolic blood pressure, Day 1, 2 Hours	1.2 Millimeters of mercury (mmHg) Standard Deviation 8.59	5.8 Millimeters of mercury (mmHg) Standard Deviation 0.35	—
Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure Systolic blood pressure, Day 4, Pre dose	1.8 Millimeters of mercury (mmHg) Standard Deviation 9.16	5.8 Millimeters of mercury (mmHg) Standard Deviation 3.18	—
Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure Systolic blood pressure, Day 7, Pre dose	-2.5 Millimeters of mercury (mmHg) Standard Deviation 11.22	-4.3 Millimeters of mercury (mmHg) Standard Deviation 8.84	—
Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure Systolic blood pressure, Day 10, Pre dose	0.6 Millimeters of mercury (mmHg) Standard Deviation 19.19	19.8 Millimeters of mercury (mmHg) Standard Deviation 14.50	—
Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure Systolic blood pressure, Day 10, 2 Hours	-0.2 Millimeters of mercury (mmHg) Standard Deviation 10.59	13.3 Millimeters of mercury (mmHg) Standard Deviation 4.60	—
Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure Diastolic blood pressure, Day 1, 2 Hours	-5.7 Millimeters of mercury (mmHg) Standard Deviation 5.76	-0.5 Millimeters of mercury (mmHg) Standard Deviation 2.12	—
Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure Diastolic blood pressure, Day 4, Pre dose	-2.4 Millimeters of mercury (mmHg) Standard Deviation 8.91	-2.5 Millimeters of mercury (mmHg) Standard Deviation 10.61	—
Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure Diastolic blood pressure, Day 7, Pre dose	-1.6 Millimeters of mercury (mmHg) Standard Deviation 9.28	-5.0 Millimeters of mercury (mmHg) Standard Deviation 15.56	—
Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure Diastolic blood pressure, Day 10, 2 Hours	-2.4 Millimeters of mercury (mmHg) Standard Deviation 6.82	6.5 Millimeters of mercury (mmHg) Standard Deviation 9.19	—

PRIMARY outcome

Timeframe: Baseline (Day 1, pre-dose) and Day 1 (2 hours post dose), 4, 7, 10

Population: Safety population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Heart rate was measured at Baseline (Day 1 pre-dose), 2 hour post dose on Day 1, pre-dose on Day 4, 7, 10 and 2 hours post dose on Day 10. Baseline was defined at Day 1 pre-dose. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo n=2 Participants Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Change From Baseline in Vital Sign: Heart Rate Day 1, 2 Hours	-7.0 Beats per minute Standard Deviation 2.10	-5.8 Beats per minute Standard Deviation 4.60	—
Change From Baseline in Vital Sign: Heart Rate Day 4, Pre dose	5.3 Beats per minute Standard Deviation 6.24	-5.8 Beats per minute Standard Deviation 1.06	—
Change From Baseline in Vital Sign: Heart Rate Day 7, Pre dose	6.3 Beats per minute Standard Deviation 5.71	-1.8 Beats per minute Standard Deviation 1.77	—
Change From Baseline in Vital Sign: Heart Rate Day 10, Pre dose	0.0 Beats per minute Standard Deviation 6.74	5.8 Beats per minute Standard Deviation 4.60	—
Change From Baseline in Vital Sign: Heart Rate Day 10, 2 Hours	-7.6 Beats per minute Standard Deviation 5.12	-10.8 Beats per minute Standard Deviation 3.18	—

PRIMARY outcome

Timeframe: Baseline (Day 1, pre-dose) and Day 1 (2 hours post dose), 4, 7, 10

Population: Safety population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

All ECGs were obtained after a minimum 10 minute rest in a semi-supine position. The 12-lead ECGs were obtained at Baseline (Day 1 pre-dose), 2 hour post dose on Day 1, pre-dose on Day 4, 7, 10 and 2 hours post dose on Day 10 using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and Bazett's correction (QTcB) and Fridericia correction (QTcF) intervals. Baseline was defined at Day 1 pre-dose. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo n=2 Participants Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Change From Baseline in Electrocardiogram (ECG) Parameters PR, Day 1, 2 Hours	0.0 Milliseconds (msec) Standard Deviation 1.83	1.0 Milliseconds (msec) Standard Deviation 2.83	—
Change From Baseline in Electrocardiogram (ECG) Parameters PR, Day 4, Pre dose	4.0 Milliseconds (msec) Standard Deviation 5.42	5.0 Milliseconds (msec) Standard Deviation 11.31	—
Change From Baseline in Electrocardiogram (ECG) Parameters PR, Day 7, Pre dose	-0.9 Milliseconds (msec) Standard Deviation 4.67	0.0 Milliseconds (msec) Standard Deviation 12.73	—
Change From Baseline in Electrocardiogram (ECG) Parameters PR, Day 10, Pre dose	-1.7 Milliseconds (msec) Standard Deviation 3.04	0.0 Milliseconds (msec) Standard Deviation 9.90	—
Change From Baseline in Electrocardiogram (ECG) Parameters PR, Day 10, 2 Hours	4.3 Milliseconds (msec) Standard Deviation 10.09	4.0 Milliseconds (msec) Standard Deviation 12.73	—
Change From Baseline in Electrocardiogram (ECG) Parameters QRS, Day 1, 2 Hours	-0.7 Milliseconds (msec) Standard Deviation 3.68	1.5 Milliseconds (msec) Standard Deviation 0.71	—
Change From Baseline in Electrocardiogram (ECG) Parameters QRS, Day 4, Pre dose	0.7 Milliseconds (msec) Standard Deviation 2.36	-3.5 Milliseconds (msec) Standard Deviation 12.02	—
Change From Baseline in Electrocardiogram (ECG) Parameters QRS, Day 7, Pre dose	-0.1 Milliseconds (msec) Standard Deviation 4.26	3.5 Milliseconds (msec) Standard Deviation 2.12	—
Change From Baseline in Electrocardiogram (ECG) Parameters QRS, Day 10, Pre dose	1.0 Milliseconds (msec) Standard Deviation 5.07	0.5 Milliseconds (msec) Standard Deviation 3.54	—
Change From Baseline in Electrocardiogram (ECG) Parameters QRS, Day 10, 2 Hours	-0.7 Milliseconds (msec) Standard Deviation 8.99	5.5 Milliseconds (msec) Standard Deviation 4.95	—
Change From Baseline in Electrocardiogram (ECG) Parameters QT, Day 1, 2 Hours	18.1 Milliseconds (msec) Standard Deviation 8.07	27.0 Milliseconds (msec) Standard Deviation 24.04	—
Change From Baseline in Electrocardiogram (ECG) Parameters QT, Day 4, Pre dose	-10.7 Milliseconds (msec) Standard Deviation 20.93	5.0 Milliseconds (msec) Standard Deviation 7.07	—
Change From Baseline in Electrocardiogram (ECG) Parameters QT, Day 7, Pre dose	-13.6 Milliseconds (msec) Standard Deviation 13.13	11.0 Milliseconds (msec) Standard Deviation 1.41	—
Change From Baseline in Electrocardiogram (ECG) Parameters QT, Day 10, Pre dose	-3.3 Milliseconds (msec) Standard Deviation 14.14	-11.0 Milliseconds (msec) Standard Deviation 24.04	—
Change From Baseline in Electrocardiogram (ECG) Parameters QT, Day 10, 2 Hours	19.0 Milliseconds (msec) Standard Deviation 22.15	25.0 Milliseconds (msec) Standard Deviation 24.04	—
Change From Baseline in Electrocardiogram (ECG) Parameters QTcB, Day 1, 2 Hours	0.2 Milliseconds (msec) Standard Deviation 13.50	6.0 Milliseconds (msec) Standard Deviation 4.09	—
Change From Baseline in Electrocardiogram (ECG) Parameters QTcB, Day 4, Pre dose	2.0 Milliseconds (msec) Standard Deviation 16.15	-17.9 Milliseconds (msec) Standard Deviation 2.20	—
Change From Baseline in Electrocardiogram (ECG) Parameters QTcB, Day 7, Pre dose	-0.0 Milliseconds (msec) Standard Deviation 16.95	-9.0 Milliseconds (msec) Standard Deviation 25.73	—
Change From Baseline in Electrocardiogram (ECG) Parameters QTcB, Day 10, Pre dose	1.4 Milliseconds (msec) Standard Deviation 16.59	-15.6 Milliseconds (msec) Standard Deviation 10.35	—
Change From Baseline in Electrocardiogram (ECG) Parameters QTcB, Day 10, 2 Hours	-2.4 Milliseconds (msec) Standard Deviation 12.35	-18.1 Milliseconds (msec) Standard Deviation 0.42	—
Change From Baseline in Electrocardiogram (ECG) Parameters QTcF, Day 1, 2 Hours	6.4 Milliseconds (msec) Standard Deviation 11.45	13.3 Milliseconds (msec) Standard Deviation 11.06	—
Change From Baseline in Electrocardiogram (ECG) Parameters QTcF, Day 4, Pre dose	-2.4 Milliseconds (msec) Standard Deviation 14.27	-10.0 Milliseconds (msec) Standard Deviation 4.05	—
Change From Baseline in Electrocardiogram (ECG) Parameters QTcF, Day 7, Pre dose	-4.7 Milliseconds (msec) Standard Deviation 13.05	-2.0 Milliseconds (msec) Standard Deviation 16.30	—
Change From Baseline in Electrocardiogram (ECG) Parameters QTcF, Day 10, Pre dose	-0.2 Milliseconds (msec) Standard Deviation 13.17	-13.9 Milliseconds (msec) Standard Deviation 15.19	—
Change From Baseline in Electrocardiogram (ECG) Parameters QTcF, Day 10, 2 Hours	4.9 Milliseconds (msec) Standard Deviation 13.62	-3.4 Milliseconds (msec) Standard Deviation 7.99	—

SECONDARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Day 1 (post dose), 2, 3, 4, 7, 8, 9, 10

Population: ITT population. Only those participants available at the indicated time points were analyzed. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Plasma for quantitative HIV-1 RNA was collected on Day 1, 2, 3, 4, 7, 8, 9, 10 and 11. On Days 1, 10 and 11, two samples for HIV-1 RNA were collected between 5-20 minutes apart to reduce sample variability. An HIV-1 RNA PCR assay with a LLOD of 50 copies/mL (ultrasensitive assay) was used for post-baseline assessments. An HIV-1 RNA PCR assay with a LLOD of 400 copies/mL (standard assay) was used for screening and Baseline assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. Baseline was defined at Day 1 (pre-dose). The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo n=2 Participants Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Change From Baseline in Plasma HIV-1 RNA Day 1	0.000 Log10 copies/mL Standard Deviation 0.0000	0.000 Log10 copies/mL Standard Deviation NA Only one participant was analyzed.	—
Change From Baseline in Plasma HIV-1 RNA Day 2	-0.126 Log10 copies/mL Standard Deviation 0.2255	0.058 Log10 copies/mL Standard Deviation 0.2303	—
Change From Baseline in Plasma HIV-1 RNA Day 3	-0.618 Log10 copies/mL Standard Deviation 0.1341	-0.299 Log10 copies/mL Standard Deviation 0.2737	—
Change From Baseline in Plasma HIV-1 RNA Day 4	-0.830 Log10 copies/mL Standard Deviation 0.2424	-0.146 Log10 copies/mL Standard Deviation 0.0580	—
Change From Baseline in Plasma HIV-1 RNA Day 7	-1.577 Log10 copies/mL Standard Deviation 0.5498	-0.168 Log10 copies/mL Standard Deviation 0.1264	—
Change From Baseline in Plasma HIV-1 RNA Day 8	-1.935 Log10 copies/mL Standard Deviation 0.4717	-0.146 Log10 copies/mL Standard Deviation 0.2779	—
Change From Baseline in Plasma HIV-1 RNA Day 9	-2.013 Log10 copies/mL Standard Deviation 0.4192	-0.007 Log10 copies/mL Standard Deviation 0.1960	—
Change From Baseline in Plasma HIV-1 RNA Day 10	-2.160 Log10 copies/mL Standard Deviation 0.2810	-0.158 Log10 copies/mL Standard Deviation 0.1930	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and Day 11

Population: ITT population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Plasma for quantitative HIV-1 RNA was collected on Day 1, 2, 3, 4, 7, 8, 9, 10 and 11. On Days 1, 10 and 11, two samples for HIV-1 RNA was collected between 5-20 minutes apart to reduce sample variability. An HIV-1 RNA PCR assay with a LLOD of 50 copies/mL (ultrasensitive assay) was used for post-baseline assessments. An HIV-1 RNA PCR assay with a LLOD of 400 copies/mL (standard assay) was used for screening and Baseline assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. Nadir was the maximum change from Baseline in plasma HIV-1 RNA. Baseline was defined at Day 1 (pre-dose). The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo n=2 Participants Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Change From Baseline in Plasma HIV-1 RNA to Nadir Over 11 Days	-2.199 log10 copies/mL Standard Deviation 0.2491	-0.418 log10 copies/mL Standard Deviation 0.1058	—

SECONDARY outcome

Timeframe: Up to Day 10

Population: ITT population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Plasma for quantitative HIV-1 RNA was collected on Day 1, 2, 3, 4, 7, 8, 9, 10 and 11. On Days 1, 10 and 11, two samples for HIV-1 RNA was collected between 5-20 minutes apart to reduce sample variability. An HIV-1 RNA PCR assay with a LLOD of 50 copies/mL (ultrasensitive assay) was used for post-baseline assessments. An HIV-1 RNA PCR assay with a LLOD of 400 copies/mL (standard assay) was used for screening and Baseline assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. Estimated mean rate of decline (i.e., slope of day) with corresponding 90% confidence interval was provided for each treatment.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo n=2 Participants Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Plasma HIV-1 RNA Rate of Decline (Slope) Over 11 Days	-0.2313 log10 copies per mL per day Interval -0.2513 to -0.2113	0.0013 log10 copies per mL per day Interval -0.0233 to 0.0259	—

SECONDARY outcome

Timeframe: Up to Day 11

Population: ITT population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Plasma for quantitative HIV-1 RNA was collected on Day 1, 2, 3, 4, 7, 8, 9, 10 and 11. On Days 1, 10 and 11, two samples for HIV-1 RNA was collected between 5-20 minutes apart to reduce sample variability. An HIV-1 RNA PCR assay with a LLOD of 50 copies/mL (ultrasensitive assay) was used for post-baseline assessments. An HIV-1 RNA PCR assay with a LLOD of 400 copies/mL (standard assay) was used for screening and Baseline assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. Only categories with data available at the indicated time points have been presented. Categories with null values for all the arms have not been presented.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo n=2 Participants Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Number of Participants With HIV-1 RNA<400 Copies/mL Day 7	2 Participants	0 Participants	—
Number of Participants With HIV-1 RNA<400 Copies/mL Day 8	4 Participants	0 Participants	—
Number of Participants With HIV-1 RNA<400 Copies/mL Day 9	4 Participants	0 Participants	—
Number of Participants With HIV-1 RNA<400 Copies/mL Day 10	5 Participants	0 Participants	—
Number of Participants With HIV-1 RNA<400 Copies/mL Day 11	5 Participants	0 Participants	—

SECONDARY outcome

Timeframe: Up to Day 11

Population: ITT population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Plasma for quantitative HIV-1 RNA was collected on Day 1, 2, 3, 4, 7, 8, 9, 10 and 11. On Days 1, 10 and 11, two samples for HIV-1 RNA was collected between 5-20 minutes apart to reduce sample variability. An HIV-1 RNA PCR assay with a LLOD of 50 copies/mL (ultrasensitive assay) was used for post-baseline assessments. An HIV-1 RNA PCR assay with a LLOD of 400 copies/mL (standard assay) was used for screening and Baseline assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. Only categories with data available at the indicated time points have been presented. Categories with null values for all the arms have not been presented.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo n=2 Participants Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Number of Participants With HIV-1 RNA<50 Copies/mL Day 8	2 Participants	0 Participants	—
Number of Participants With HIV-1 RNA<50 Copies/mL Day 9	3 Participants	0 Participants	—
Number of Participants With HIV-1 RNA<50 Copies/mL Day 10	2 Participants	0 Participants	—
Number of Participants With HIV-1 RNA<50 Copies/mL Day 11	2 Participants	0 Participants	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and Day 11

Population: ITT population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Whole venous blood samples was obtained from each participant for the analysis of lymphocyte subsets by flow cytometry on Day 1 and Day 11. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo n=2 Participants Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Change From Baseline in CD4+ Cell Count to Day 11	71.0 Cells per cubic millimeter Standard Deviation 56.62	-84.0 Cells per cubic millimeter Standard Deviation 145.66	—

SECONDARY outcome

Timeframe: Day 1 24 hours (Day 2), Pre-dose on Days 3, 4, 7, 8, 9 and 10

Population: ITT population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

Steady state is said to be reached, when the pre-dose concentration slope estimate is close to zero. The data for pre-dose concentration on Day 1 24 hours (Day 2) through Day 10 has been presented.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Pre-morning Dose Concentrations (C0) on Day 2 Through 10 to Assess the Achievement of Steady State of GSK1265744 Following Repeat Administration DAY 1, 24 hours (Day 2)	0.2363 µg/mL Standard Deviation 0.06884	—	—
Pre-morning Dose Concentrations (C0) on Day 2 Through 10 to Assess the Achievement of Steady State of GSK1265744 Following Repeat Administration DAY 3, Pre-dose	0.3539 µg/mL Standard Deviation 0.12999	—	—
Pre-morning Dose Concentrations (C0) on Day 2 Through 10 to Assess the Achievement of Steady State of GSK1265744 Following Repeat Administration DAY 4, Pre-dose	0.4128 µg/mL Standard Deviation 0.15566	—	—
Pre-morning Dose Concentrations (C0) on Day 2 Through 10 to Assess the Achievement of Steady State of GSK1265744 Following Repeat Administration DAY 7, Pre-dose	0.5239 µg/mL Standard Deviation 0.11899	—	—
Pre-morning Dose Concentrations (C0) on Day 2 Through 10 to Assess the Achievement of Steady State of GSK1265744 Following Repeat Administration DAY 8, Pre-dose	0.5744 µg/mL Standard Deviation 0.17622	—	—
Pre-morning Dose Concentrations (C0) on Day 2 Through 10 to Assess the Achievement of Steady State of GSK1265744 Following Repeat Administration DAY 9, Pre-dose	0.5688 µg/mL Standard Deviation 0.16880	—	—
Pre-morning Dose Concentrations (C0) on Day 2 Through 10 to Assess the Achievement of Steady State of GSK1265744 Following Repeat Administration DAY 10, Pre-dose	0.5654 µg/mL Standard Deviation 0.20609	—	—

SECONDARY outcome

Timeframe: Days 1 and 10

Population: PK/ Pharmacodynamic (PD) Summary Population included participants who met the criteria for both ITT Population and PK Summary Population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.

The accumulation ratio was calculated as the ratio of AUC(0-τ), Cmax, and Ctau on Day 10 to AUC(0-24), Cmax, and C24 on Day 1 for each participant. The ratio of geometric least square means of each parameter on Day 10 to Day 1 was presented along with 90% confidence interval.

Outcome measures

Measure	GSK1265744 5 mg n=7 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Accumulation Ratios for AUC, Cmax, and Ctau Accumulation Ratio AUC	2.355 Ratio Interval 2.086 to 2.658	—	—
Accumulation Ratios for AUC, Cmax, and Ctau Accumulation Ratio Cmax	1.961 Ratio Interval 1.684 to 2.283	—	—
Accumulation Ratios for AUC, Cmax, and Ctau Accumulation Ratio Ctau	2.483 Ratio Interval 2.141 to 2.88	—	—

SECONDARY outcome

Timeframe: Day 1

Population: PK Summary Population.

Data from GSK1265744 30 mg in HIV participants (Study ITZ111451 part C HIV cohort, NCT00659191) was combined with data from this study to access dose proportionality. Dose proportionality of GSK1265744 PK parameters was assessed following single dose administration on Day 1 (AUC[0-24]) using the power model. The mean slope and corresponding 90% confidence interval has been presented.

Outcome measures

Measure	GSK1265744 5 mg n=15 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Day 1 AUC(0-24) at Different Doses for the Assessment of Dose Proportionality Using Power Model	0.952 hr*µg/mL/mg Interval 0.802 to 1.101	—	—

SECONDARY outcome

Timeframe: Day 1

Population: PK Summary Population.

Data from GSK1265744 30 mg in HIV participants (Study ITZ111451 part C HIV cohort, NCT00659191) was combined with data from this study to access dose proportionality. Dose proportionality of GSK1265744 PK parameters was assessed following single dose administration on Day 1 (Cmax, and C24) using the power model. The mean slope and corresponding 90% confidence interval has been presented.

Outcome measures

Measure	GSK1265744 5 mg n=15 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Day 1 Cmax and C24 at Different Doses for the Assessment of Dose Proportionality Using Power Model Cmax	0.950 μg/mL/mg Interval 0.812 to 1.088	—	—
Day 1 Cmax and C24 at Different Doses for the Assessment of Dose Proportionality Using Power Model C24	0.949 μg/mL/mg Interval 0.777 to 1.121	—	—

SECONDARY outcome

Timeframe: Day 10

Population: PK Summary Population.

Data from GSK1265744 30 mg in HIV participants (Study ITZ111451 part C HIV cohort, NCT00659191) was combined with data from this study to access dose proportionality. Dose proportionality of GSK1265744 PK parameters was assessed following a repeat dose administration on Day 10 (AUC[0-tau]) using the power model. The mean slope and corresponding 90% confidence interval has been presented.

Outcome measures

Measure	GSK1265744 5 mg n=15 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Day 10 AUC(0-tau) at Different Doses for the Assessment of Dose Proportionality Using Power Model	0.988 hr*µg/mL/mg Interval 0.841 to 1.135	—	—

SECONDARY outcome

Timeframe: Day 10

Population: PK Summary Population.

Data from GSK1265744 30 mg in HIV participants (Study ITZ111451 part C HIV cohort, NCT00659191) was combined with data from this study to access dose proportionality. Dose proportionality of GSK1265744 PK parameters was assessed following a repeat dose administration on Day 10 (Cmax, Ctau and C0) using the power model. The mean slope and corresponding 90% confidence interval has been presented.

Outcome measures

Measure	GSK1265744 5 mg n=15 Participants Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days.	Placebo Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days.	Optimized Therapy Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Day 10 Cmax, C0 and Ctau at Different Doses for the Assessment of Dose Proportionality Using Power Model Cmax	1.025 µg/mL/mg Interval 0.903 to 1.147	—	—
Day 10 Cmax, C0 and Ctau at Different Doses for the Assessment of Dose Proportionality Using Power Model C0	0.936 µg/mL/mg Interval 0.761 to 1.11	—	—
Day 10 Cmax, C0 and Ctau at Different Doses for the Assessment of Dose Proportionality Using Power Model Ctau	0.980 µg/mL/mg Interval 0.808 to 1.151	—	—

Adverse Events

GSK1265744 30 mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

GSK1265744 5 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Optimized Therapy

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	GSK1265744 30 mg n=8 participants at risk GSK1265744 30 mg once daily was previously studied in study ITZ111451 part C HIV cohort, NCT00659191. Eligible participants received repeat doses of GSK1265744 30 mg (6x5 mg) oral tablets once daily for 10 days.	GSK1265744 5 mg n=7 participants at risk Eligible participants received double-blind 5 mg GSK1265744 oral tablet once daily for 10 days.	Placebo n=2 participants at risk Eligible participants received double-blind Placebo matching 5 mg GSK1265744 oral tablet once daily for 10 days.	Optimized Therapy n=8 participants at risk Participants were given investigator chosen optimized therapy for 14 days after being dosed with the randomized regimen (either 5 mg GSK1265744 or Placebo) for 10 days. Participants were unblinded on Day 11 so that the participants receiving Placebo could decline optimized therapy.
Gastrointestinal disorders Nausea	0.00% 0/8 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/7 • Up to follow-up visit (Day 25±1) Safety Population was used.	50.0% 1/2 • Up to follow-up visit (Day 25±1) Safety Population was used.	12.5% 1/8 • Up to follow-up visit (Day 25±1) Safety Population was used.
Investigations Blood bilirubin increased	0.00% 0/8 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/7 • Up to follow-up visit (Day 25±1) Safety Population was used.	50.0% 1/2 • Up to follow-up visit (Day 25±1) Safety Population was used.	12.5% 1/8 • Up to follow-up visit (Day 25±1) Safety Population was used.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/8 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/7 • Up to follow-up visit (Day 25±1) Safety Population was used.	50.0% 1/2 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/8 • Up to follow-up visit (Day 25±1) Safety Population was used.
Gastrointestinal disorders Abdominal pain	0.00% 0/8 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/7 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/2 • Up to follow-up visit (Day 25±1) Safety Population was used.	12.5% 1/8 • Up to follow-up visit (Day 25±1) Safety Population was used.
Gastrointestinal disorders Constipation	0.00% 0/8 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/7 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/2 • Up to follow-up visit (Day 25±1) Safety Population was used.	12.5% 1/8 • Up to follow-up visit (Day 25±1) Safety Population was used.
Eye disorders Ocular icterus	0.00% 0/8 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/7 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/2 • Up to follow-up visit (Day 25±1) Safety Population was used.	12.5% 1/8 • Up to follow-up visit (Day 25±1) Safety Population was used.
Nervous system disorders Headache	25.0% 2/8 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/7 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/2 • Up to follow-up visit (Day 25±1) Safety Population was used.	12.5% 1/8 • Up to follow-up visit (Day 25±1) Safety Population was used.
Nervous system disorders Dizziness	37.5% 3/8 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/7 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/2 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/8 • Up to follow-up visit (Day 25±1) Safety Population was used.
Nervous system disorders Somnolence	12.5% 1/8 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/7 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/2 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/8 • Up to follow-up visit (Day 25±1) Safety Population was used.
General disorders Fatigue	12.5% 1/8 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/7 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/2 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/8 • Up to follow-up visit (Day 25±1) Safety Population was used.
Gastrointestinal disorders Dyspepsia	25.0% 2/8 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/7 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/2 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/8 • Up to follow-up visit (Day 25±1) Safety Population was used.
Psychiatric disorders Abnormal dreams	12.5% 1/8 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/7 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/2 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/8 • Up to follow-up visit (Day 25±1) Safety Population was used.
Vascular disorders Hot flush	12.5% 1/8 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/7 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/2 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/8 • Up to follow-up visit (Day 25±1) Safety Population was used.
Hepatobiliary disorders Jaundice	12.5% 1/8 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/7 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/2 • Up to follow-up visit (Day 25±1) Safety Population was used.	0.00% 0/8 • Up to follow-up visit (Day 25±1) Safety Population was used.

Additional Information

GSK Response Center

ViiV Healthcare

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