Trial Outcomes & Findings for Dose-finding Study of GSK2248761 in Antiretroviral Therapy-Naive Subjects (SIGNET) (NCT NCT01231555)

Last Updated: 2017-11-17

Results Overview

This analysis was based on the Missing, Switch or Discontinuation equals Failure (MSDF) algorithm (as codified by the FDA's "snapshot" algorithm) and was adjusted for stratification factors and stage of recruitment. Dose selection was based primarily on antiviral activity and tolerability in conjunction with immunologic, safety, virologic resistance and pharmacokinetic (PK) measures. The efficacy decision criteria was based on an observed difference of \>=8% between the two GSK2248761 dosage arms.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

23 participants

Primary outcome timeframe

Up to Week 16

Results posted on

2017-11-17

Participant Flow

This study was conducted from 18 November 2010 to 04 July 2011. A total of 150 human immunodeficiency virus (HIV)-1 infected adult participants naïve to antiretroviral therapy (ART) were planned to be enrolled.

Enrollment was terminated prematurely due to safety findings. At the time of enrollment termination, 23 participants were enrolled who continued into this study. At least 5 interim analyses were planned up to Week 48, however, the study was terminated prior to any of these analyses being conducted.

Participant milestones

Participant milestones
Measure	GSK2248761 100 mg Once Daily Eligible participants were planned to receive oral GSK2248761 100 milligrams (mg) capsule once daily and matching GSK2248761 Placebo capsule once daily up to 48 weeks, however, participants received GSK2248761 100 mg once daily and matching GSK2248761 Placebo capsule once daily up to 8 weeks due to early termination. All participants received antiretroviral therapy (ART) of Tenofovir disoproxil fumarate/ Emtricitabine (TDF/FTC) 300 mg/200 mg or Abacavir/ Lamivudine (ABC/3TC) 600 mg/300 mg along with the study drug.	GSK2248761 200 mg Once Daily Eligible participants were planned to receive oral GSK2248761 200 mg (2x100 mg) capsule once daily up to 48 weeks, however, participants received GSK2248761 200 mg oral capsule once daily up to 8 weeks due early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.	EFV 600 mg Once Daily Eligible participants were planned to receive oral Efavirenz (EFV) 600 mg tablet once daily up to 48 weeks, however participants received EFV 600 mg tablet once daily up to 16 weeks due to early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.
Overall Study STARTED	8	7	8
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	8	7	8

Reasons for withdrawal

Reasons for withdrawal
Measure	GSK2248761 100 mg Once Daily Eligible participants were planned to receive oral GSK2248761 100 milligrams (mg) capsule once daily and matching GSK2248761 Placebo capsule once daily up to 48 weeks, however, participants received GSK2248761 100 mg once daily and matching GSK2248761 Placebo capsule once daily up to 8 weeks due to early termination. All participants received antiretroviral therapy (ART) of Tenofovir disoproxil fumarate/ Emtricitabine (TDF/FTC) 300 mg/200 mg or Abacavir/ Lamivudine (ABC/3TC) 600 mg/300 mg along with the study drug.	GSK2248761 200 mg Once Daily Eligible participants were planned to receive oral GSK2248761 200 mg (2x100 mg) capsule once daily up to 48 weeks, however, participants received GSK2248761 200 mg oral capsule once daily up to 8 weeks due early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.	EFV 600 mg Once Daily Eligible participants were planned to receive oral Efavirenz (EFV) 600 mg tablet once daily up to 48 weeks, however participants received EFV 600 mg tablet once daily up to 16 weeks due to early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.
Overall Study Study terminated	8	5	8
Overall Study Withdrawal by Subject	0	2	0

Baseline Characteristics

Dose-finding Study of GSK2248761 in Antiretroviral Therapy-Naive Subjects (SIGNET)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GSK2248761 100 mg Once Daily n=8 Participants Eligible participants were planned to receive oral GSK2248761 100 mg capsule once daily and matching GSK2248761 Placebo capsule once daily up to 48 weeks, however, participants received GSK2248761 100 once daily and matching GSK2248761 Placebo capsule once daily up to 8 weeks due to early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.	GSK2248761 200 mg Once Daily n=7 Participants Eligible participants were planned to receive oral GSK2248761 200 mg (2x100 mg) capsule once daily up to 48 weeks, however, participants received GSK2248761 200 mg oral capsule once daily up to 8 weeks due early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.	EFV 600 mg Once Daily n=8 Participants Eligible participants were planned to receive oral EFV 600 mg tablet once daily up to 48 weeks, however participants received EFV 600 mg tablet once daily up to 16 weeks due to early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.	Total n=23 Participants Total of all reporting groups
Age, Continuous	38.8 Years STANDARD_DEVIATION 8.01 • n=93 Participants	35.9 Years STANDARD_DEVIATION 6.47 • n=4 Participants	35.9 Years STANDARD_DEVIATION 7.97 • n=27 Participants	36.9 Years STANDARD_DEVIATION 7.35 • n=483 Participants
Sex: Female, Male Female	0 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants
Sex: Female, Male Male	8 Participants n=93 Participants	6 Participants n=4 Participants	8 Participants n=27 Participants	22 Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants
Race (NIH/OMB) White	7 Participants n=93 Participants	7 Participants n=4 Participants	8 Participants n=27 Participants	22 Participants n=483 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants

PRIMARY outcome

Timeframe: Up to Week 16

Population: Intent to treat exposed (ITT-E) population included all randomized participants who received at least one dose of study drug. Data points with null value for participants analyzed indicate data not collected for respective category and treatment arm due to early termination. Only those participants available at indicated timepoints were analyzed.

Outcome measures

Outcome measures
Measure	GSK2248761 100 mg Once Daily n=8 Participants Eligible participants were planned to receive oral GSK2248761 100 mg capsule once daily and matching GSK2248761 Placebo capsule once daily up to 48 weeks, however, participants received GSK2248761 100 once daily and matching GSK2248761 Placebo capsule once daily up to 8 weeks due to early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.	GSK2248761 200 mg Once Daily n=7 Participants Eligible participants were planned to receive oral GSK2248761 200 mg (2x100 mg) capsule once daily up to 48 weeks, however, participants received GSK2248761 200 mg oral capsule once daily up to 8 weeks due early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.	EFV 600 mg Once Daily n=8 Participants Eligible participants were planned to receive oral EFV 600 mg tablet once daily up to 48 weeks, however participants received EFV 600 mg tablet once daily up to 16 weeks due to early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.
Number of Participants With Plasma HIV-1 RNA Below 50 Copies/mL as a Function of Viral Load Before switch, Week 4	1 Participants	0 Participants	3 Participants
Number of Participants With Plasma HIV-1 RNA Below 50 Copies/mL as a Function of Viral Load Before switch, Week 8	—	1 Participants	3 Participants
Number of Participants With Plasma HIV-1 RNA Below 50 Copies/mL as a Function of Viral Load Before switch, Week 12	—	—	2 Participants
Number of Participants With Plasma HIV-1 RNA Below 50 Copies/mL as a Function of Viral Load After switch, Baseline switch	1 Participants	1 Participants	—
Number of Participants With Plasma HIV-1 RNA Below 50 Copies/mL as a Function of Viral Load After switch, Week 1	3 Participants	1 Participants	—
Number of Participants With Plasma HIV-1 RNA Below 50 Copies/mL as a Function of Viral Load After switch, Week 2	3 Participants	1 Participants	—
Number of Participants With Plasma HIV-1 RNA Below 50 Copies/mL as a Function of Viral Load After switch, Week 4	2 Participants	1 Participants	—

PRIMARY outcome

Timeframe: Up to 20 Weeks

Population: Safety population included all randomized participants who were exposed to the study drug(s) with the exception of any participant with documented evidence of not having consumed any amount of the study drug.

Adverse event (AE) is an unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain time period after the study has ended. This change may or may not be caused by the intervention being studied. Serious adverse event (SAE) is an adverse event that results in death, is life-threatening, requires inpatient hospitalization or extends a current hospital stay, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect. Medical events that do not result in death, are not life-threatening, or do not require hospitalization may be considered serious adverse events if they put the participant in danger or require medical or surgical intervention to prevent one of the results listed above.

Outcome measures

Outcome measures
Measure	GSK2248761 100 mg Once Daily n=8 Participants Eligible participants were planned to receive oral GSK2248761 100 mg capsule once daily and matching GSK2248761 Placebo capsule once daily up to 48 weeks, however, participants received GSK2248761 100 once daily and matching GSK2248761 Placebo capsule once daily up to 8 weeks due to early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.	GSK2248761 200 mg Once Daily n=7 Participants Eligible participants were planned to receive oral GSK2248761 200 mg (2x100 mg) capsule once daily up to 48 weeks, however, participants received GSK2248761 200 mg oral capsule once daily up to 8 weeks due early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.	EFV 600 mg Once Daily n=8 Participants Eligible participants were planned to receive oral EFV 600 mg tablet once daily up to 48 weeks, however participants received EFV 600 mg tablet once daily up to 16 weeks due to early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.
Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs) Any SAE	1 Participants	0 Participants	1 Participants
Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs) Any AE	8 Participants	5 Participants	8 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) up to Week 16

Population: ITT-E population. Data for only those participants available at the indicated time points were collected and analyzed. Data points with null value for participants analyzed indicate data not collected for respective category and treatment arm due to early termination.

For summaries and analyses which use HIV-1 RNA level as a continuous measure, the logarithm to base 10 of the value was used. In cases where a sample was retested, the retest value was used. Baseline was defined as the value recorded on Day 1. Change from Baseline is the value at indicated time point minus the Baseline value. Data for participants prior to switch and after the switch has been presented.

Outcome measures

Outcome measures
Measure	GSK2248761 100 mg Once Daily n=8 Participants Eligible participants were planned to receive oral GSK2248761 100 mg capsule once daily and matching GSK2248761 Placebo capsule once daily up to 48 weeks, however, participants received GSK2248761 100 once daily and matching GSK2248761 Placebo capsule once daily up to 8 weeks due to early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.	GSK2248761 200 mg Once Daily n=7 Participants Eligible participants were planned to receive oral GSK2248761 200 mg (2x100 mg) capsule once daily up to 48 weeks, however, participants received GSK2248761 200 mg oral capsule once daily up to 8 weeks due early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.	EFV 600 mg Once Daily n=8 Participants Eligible participants were planned to receive oral EFV 600 mg tablet once daily up to 48 weeks, however participants received EFV 600 mg tablet once daily up to 16 weeks due to early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.
Change From Baseline (Day 1) in Plasma HIV-1 RNA Over Period Before switch, Week 2	-1.863 log10 copies per milliliter Standard Deviation 0.3496	-2.018 log10 copies per milliliter Standard Deviation 0.3427	-2.131 log10 copies per milliliter Standard Deviation 0.2818
Change From Baseline (Day 1) in Plasma HIV-1 RNA Over Period Before switch, Week 4	-2.140 log10 copies per milliliter Standard Deviation 0.4528	-2.134 log10 copies per milliliter Standard Deviation 0.3055	-2.334 log10 copies per milliliter Standard Deviation 0.3384
Change From Baseline (Day 1) in Plasma HIV-1 RNA Over Period Before switch, Week 8	—	-2.712 log10 copies per milliliter Standard Deviation NA Only one participant was analyzed.	-2.723 log10 copies per milliliter Standard Deviation 0.2411
Change From Baseline (Day 1) in Plasma HIV-1 RNA Over Period Before switch, Week 12	—	—	-2.866 log10 copies per milliliter Standard Deviation 0.2909
Change From Baseline (Day 1) in Plasma HIV-1 RNA Over Period Baseline switch	-2.046 log10 copies per milliliter Standard Deviation 0.4943	-2.170 log10 copies per milliliter Standard Deviation 0.4990	—
Change From Baseline (Day 1) in Plasma HIV-1 RNA Over Period After switch, Week 1	-2.218 log10 copies per milliliter Standard Deviation 0.5211	-2.287 log10 copies per milliliter Standard Deviation 0.4812	—
Change From Baseline (Day 1) in Plasma HIV-1 RNA Over Period After switch, Week 2	-2.307 log10 copies per milliliter Standard Deviation 0.4219	-2.235 log10 copies per milliliter Standard Deviation 0.3383	—
Change From Baseline (Day 1) in Plasma HIV-1 RNA Over Period After switch, Week 4	-2.380 log10 copies per milliliter Standard Deviation 0.2749	-2.482 log10 copies per milliliter Standard Deviation 0.2567	—

SECONDARY outcome

Timeframe: Up to 20 Weeks

Population: ITT-E population.

HIV associated condition included recurrence of previous conditions. Centre for disease control (CDC) associated conditions and non-CDC associated conditions were planned to be monitored.

Outcome measures

Outcome measures
Measure	GSK2248761 100 mg Once Daily n=8 Participants Eligible participants were planned to receive oral GSK2248761 100 mg capsule once daily and matching GSK2248761 Placebo capsule once daily up to 48 weeks, however, participants received GSK2248761 100 once daily and matching GSK2248761 Placebo capsule once daily up to 8 weeks due to early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.	GSK2248761 200 mg Once Daily n=7 Participants Eligible participants were planned to receive oral GSK2248761 200 mg (2x100 mg) capsule once daily up to 48 weeks, however, participants received GSK2248761 200 mg oral capsule once daily up to 8 weeks due early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.	EFV 600 mg Once Daily n=8 Participants Eligible participants were planned to receive oral EFV 600 mg tablet once daily up to 48 weeks, however participants received EFV 600 mg tablet once daily up to 16 weeks due to early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.
Number of Participants With HIV Associated Conditions	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 20 Weeks

Population: ITT-E population.

Number of participants acquiring clinical disease progression or death during the treatment period were presented. Clinical disease progression was defined as the progression from Baseline (Day 1) HIV disease status in either of these categories; CDC Category A at baseline to CDC Category B event, CDC Category A at baseline to CDC Category C event, CDC Category B at baseline to CDC Category C event, CDC Category C at baseline to new CDC Category C event, CDC Category A, B or C at baseline to death. If no change occurs, it was termed as no disease progression.

Outcome measures

Outcome measures
Measure	GSK2248761 100 mg Once Daily n=8 Participants Eligible participants were planned to receive oral GSK2248761 100 mg capsule once daily and matching GSK2248761 Placebo capsule once daily up to 48 weeks, however, participants received GSK2248761 100 once daily and matching GSK2248761 Placebo capsule once daily up to 8 weeks due to early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.	GSK2248761 200 mg Once Daily n=7 Participants Eligible participants were planned to receive oral GSK2248761 200 mg (2x100 mg) capsule once daily up to 48 weeks, however, participants received GSK2248761 200 mg oral capsule once daily up to 8 weeks due early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.	EFV 600 mg Once Daily n=8 Participants Eligible participants were planned to receive oral EFV 600 mg tablet once daily up to 48 weeks, however participants received EFV 600 mg tablet once daily up to 16 weeks due to early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.
Number of Participants With HIV Disease Progression	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 20 weeks

Population: Safety population

Outcome measures

Outcome measures
Measure	GSK2248761 100 mg Once Daily n=8 Participants Eligible participants were planned to receive oral GSK2248761 100 mg capsule once daily and matching GSK2248761 Placebo capsule once daily up to 48 weeks, however, participants received GSK2248761 100 once daily and matching GSK2248761 Placebo capsule once daily up to 8 weeks due to early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.	GSK2248761 200 mg Once Daily n=7 Participants Eligible participants were planned to receive oral GSK2248761 200 mg (2x100 mg) capsule once daily up to 48 weeks, however, participants received GSK2248761 200 mg oral capsule once daily up to 8 weeks due early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.	EFV 600 mg Once Daily n=8 Participants Eligible participants were planned to receive oral EFV 600 mg tablet once daily up to 48 weeks, however participants received EFV 600 mg tablet once daily up to 16 weeks due to early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.
Number of Participants Discontinuing the Study Drugs Due to AEs	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to 16 weeks

Population: Safety population. Data for only those participants available at the indicated time points were collected and analyzed. Data points with null value for participants analyzed indicate data not collected for respective category and treatment arm due to early termination.

The QTc interval was assessed by two methods Bazzette's method (QTc\[b\]) and Federica's method (QTc\[f\]). Baseline value was recorded at Day 1. Change from Baseline is the value at indicated time point minus the Baseline value. Change from Baseline values were categorized into \<30 milliseconds (msec), \>=30 but \<60 msec, and \>=60 msec. The data has been presented for QTcB and QTcF for participants prior to switching the therapy.

Outcome measures

Outcome measures
Measure	GSK2248761 100 mg Once Daily n=8 Participants Eligible participants were planned to receive oral GSK2248761 100 mg capsule once daily and matching GSK2248761 Placebo capsule once daily up to 48 weeks, however, participants received GSK2248761 100 once daily and matching GSK2248761 Placebo capsule once daily up to 8 weeks due to early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.	GSK2248761 200 mg Once Daily n=7 Participants Eligible participants were planned to receive oral GSK2248761 200 mg (2x100 mg) capsule once daily up to 48 weeks, however, participants received GSK2248761 200 mg oral capsule once daily up to 8 weeks due early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.	EFV 600 mg Once Daily n=8 Participants Eligible participants were planned to receive oral EFV 600 mg tablet once daily up to 48 weeks, however participants received EFV 600 mg tablet once daily up to 16 weeks due to early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.
Number of Participants With Changes in Electrocardiogram (ECG) From Baseline (Day 1) Over 16 Weeks QTcF, Week 4, <30 msec	4 Participants	4 Participants	6 Participants
Number of Participants With Changes in Electrocardiogram (ECG) From Baseline (Day 1) Over 16 Weeks QTcF, Week 12, <30 msec	—	—	2 Participants
Number of Participants With Changes in Electrocardiogram (ECG) From Baseline (Day 1) Over 16 Weeks QTcF, Week 12, >=30 to <60	—	—	1 Participants
Number of Participants With Changes in Electrocardiogram (ECG) From Baseline (Day 1) Over 16 Weeks QTcB, Week 2, <30 msec	6 Participants	5 Participants	7 Participants
Number of Participants With Changes in Electrocardiogram (ECG) From Baseline (Day 1) Over 16 Weeks QTcB, Week 2, >=30 to <60 msec	0 Participants	0 Participants	1 Participants
Number of Participants With Changes in Electrocardiogram (ECG) From Baseline (Day 1) Over 16 Weeks QTcB, Week 4, <30 msec	4 Participants	4 Participants	6 Participants
Number of Participants With Changes in Electrocardiogram (ECG) From Baseline (Day 1) Over 16 Weeks QTcB, Week 12, <30 msec	—	—	3 Participants
Number of Participants With Changes in Electrocardiogram (ECG) From Baseline (Day 1) Over 16 Weeks QTcF, Week 2, <30 msec	6 Participants	5 Participants	8 Participants

SECONDARY outcome

Timeframe: At Week 2

Population: The PK Concentration Population included all participants who received GSK2248761, underwent intensive and/or limited PK sampling during the study, and provided evaluable GSK2248761 plasma concentration data. Only the participants available at the time of assessment were analyzed.

Maximum observed plasma concentration and minimum observed plasma concentration of GSK2248761 was recorded on Week 2. The PK parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Pro 4.1 or higher. Log transformed values have been presented. All calculations of non-compartmental parameters were based on actual sampling times.

Outcome measures

Outcome measures
Measure	GSK2248761 100 mg Once Daily n=8 Participants Eligible participants were planned to receive oral GSK2248761 100 mg capsule once daily and matching GSK2248761 Placebo capsule once daily up to 48 weeks, however, participants received GSK2248761 100 once daily and matching GSK2248761 Placebo capsule once daily up to 8 weeks due to early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.	GSK2248761 200 mg Once Daily n=7 Participants Eligible participants were planned to receive oral GSK2248761 200 mg (2x100 mg) capsule once daily up to 48 weeks, however, participants received GSK2248761 200 mg oral capsule once daily up to 8 weeks due early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.	EFV 600 mg Once Daily Eligible participants were planned to receive oral EFV 600 mg tablet once daily up to 48 weeks, however participants received EFV 600 mg tablet once daily up to 16 weeks due to early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.
Minimum and Maximum Plasma GSK2248761 Concentration at Week 2 Cmin	0.15 micrograms per milliliter Geometric Coefficient of Variation 149	0.49 micrograms per milliliter Geometric Coefficient of Variation 164	—
Minimum and Maximum Plasma GSK2248761 Concentration at Week 2 Cmax	1.78 micrograms per milliliter Geometric Coefficient of Variation 39	3.70 micrograms per milliliter Geometric Coefficient of Variation 40	—

Adverse Events

GSK2248761 100 mg Once Daily

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

GSK2248761 200 mg Once Daily

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

EFV 600 mg Once Daily

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	GSK2248761 100 mg Once Daily n=8 participants at risk Eligible participants were planned to receive oral GSK2248761 100 mg capsule once daily and matching GSK2248761 Placebo capsule once daily up to 48 weeks, however, participants received GSK2248761 100 once daily and matching GSK2248761 Placebo capsule once daily up to 8 weeks due to early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.	GSK2248761 200 mg Once Daily n=7 participants at risk Eligible participants were planned to receive oral GSK2248761 200 mg (2x100 mg) capsule once daily up to 48 weeks, however, participants received GSK2248761 200 mg oral capsule once daily up to 8 weeks due early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.	EFV 600 mg Once Daily n=8 participants at risk Eligible participants were planned to receive oral EFV 600 mg tablet once daily up to 48 weeks, however participants received EFV 600 mg tablet once daily up to 16 weeks due to early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.
Infections and infestations Clostridium difficile colitis	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Skin and subcutaneous tissue disorders Toxic skin eruption	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population

Other adverse events

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

Measure	GSK2248761 100 mg Once Daily n=8 participants at risk Eligible participants were planned to receive oral GSK2248761 100 mg capsule once daily and matching GSK2248761 Placebo capsule once daily up to 48 weeks, however, participants received GSK2248761 100 once daily and matching GSK2248761 Placebo capsule once daily up to 8 weeks due to early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.	GSK2248761 200 mg Once Daily n=7 participants at risk Eligible participants were planned to receive oral GSK2248761 200 mg (2x100 mg) capsule once daily up to 48 weeks, however, participants received GSK2248761 200 mg oral capsule once daily up to 8 weeks due early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.	EFV 600 mg Once Daily n=8 participants at risk Eligible participants were planned to receive oral EFV 600 mg tablet once daily up to 48 weeks, however participants received EFV 600 mg tablet once daily up to 16 weeks due to early termination. All participants received ART of TDF/FTC 300 mg/200 mg or ABC/3TC 600 mg/300 mg along with the study drug.
Nervous system disorders Dizziness	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	75.0% 6/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Nervous system disorders Somnolence	25.0% 2/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	28.6% 2/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Nervous system disorders Headache	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	28.6% 2/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Nervous system disorders Circadian rhythm sleep disorder	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Nervous system disorders Depressed level of consciousness	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Nervous system disorders Hypoaesthesia	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Nervous system disorders Migraine	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Infections and infestations Nasopharyngitis	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	37.5% 3/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Infections and infestations Bronchitis	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	28.6% 2/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Infections and infestations Anogenital warts	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	25.0% 2/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Infections and infestations Rhinitis	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	14.3% 1/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Infections and infestations Sinusitis	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	14.3% 1/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Infections and infestations Anal chlamydia infection	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Infections and infestations Erysipelas	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Infections and infestations Gastroenteritis	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Infections and infestations Laryngitis	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Infections and infestations Pharyngitis	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Infections and infestations Syphilis	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Psychiatric disorders Nightmare	25.0% 2/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	42.9% 3/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	37.5% 3/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Psychiatric disorders Abnormal dreams	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	25.0% 2/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Psychiatric disorders Anxiety	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Psychiatric disorders Depressed mood	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	14.3% 1/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Psychiatric disorders Depression	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	14.3% 1/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Psychiatric disorders Insomnia	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	14.3% 1/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Psychiatric disorders Sleep disorder	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Gastrointestinal disorders Diarrhoea	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	25.0% 2/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Gastrointestinal disorders Nausea	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	25.0% 2/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Gastrointestinal disorders Rectal haemorrhage	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Gastrointestinal disorders Dry mouth	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Gastrointestinal disorders Flatulence	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Gastrointestinal disorders Gingival bleeding	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	14.3% 1/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Skin and subcutaneous tissue disorders Pruritus	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	14.3% 1/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Skin and subcutaneous tissue disorders Night sweats	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	14.3% 1/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Skin and subcutaneous tissue disorders Rash	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Skin and subcutaneous tissue disorders Rash papular	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Skin and subcutaneous tissue disorders Toxic skin eruption	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Ear and labyrinth disorders Vertigo	37.5% 3/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	25.0% 2/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
General disorders Fatigue	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
General disorders Asthenia	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	14.3% 1/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
General disorders Chest pain	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
General disorders Feeling abnormal	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	14.3% 1/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Eye disorders Blindness	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Eye disorders Conjunctivitis	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	25.0% 2/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Cardiac disorders Palpitations	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Injury, poisoning and procedural complications Procedural pain	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population
Metabolism and nutrition disorders Lactose intolerance	0.00% 0/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	0.00% 0/7 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population	12.5% 1/8 • Up to 20 weeks AE (SAE and nSAE) were collected and have been reported for safety population