Trial Outcomes & Findings for Dose-finding Study of GSK2248761 in Antiretroviral Therapy-experienced Subjects With NNRTI-resistant HIV Infection (NCT NCT01199731)

NCT ID: NCT01199731

Last Updated: 2017-11-17

Results Overview

Plasma for quantitative HIV-1 RNA was collected. The percentage of participants with HIV-1 RNA \<50 copies/mL at Week 16 has been presented. A 2 ml plasma was assayed with the real-time NucliSens EasyQ HIV-1 assay (bioMerieux) capable of quantifying as low as 2.5 c/mL by using three modifications to the standard assay: 15 microliters (µl) of extracted eluate, 20 µl of primer, and 5 µl of 2X enzyme in place of standard kit volumes. The validated assay incorporated molecular beacons for detection.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

30 participants

Primary outcome timeframe

At Week 16

Results posted on

2017-11-17

Participant Flow

A total of 17 investigational sites enrolled participants in this multicenter study: 1 center in Romania and 16 in the United States. The study was initiated on 04 October 2010 and was terminated on 01 April 2011 with last participant visit on 19 July 2011.

Enrollment in this study was terminated prematurely due to a safety finding (convulsions) in 5/20 participants who received GSK2248761. At time of enrollment termination, 30/150 planned participants were enrolled.

Participant milestones

Participant milestones
Measure	GSK2248761 100 Milligram (mg) Participants received GSK2248761 1 x 100 mg capsule once daily orally, 1 x Placebo to match GSK2248761 capsule once daily orally, Darunavir (DRV) 1 x 600 mg tablet twice daily with food orally, Ritonavir (RTV) 1 x 100 mg tablet twice daily orally and Raltegravir(RAL) 1 x 400 mg tablet twice daily orally up to 48 weeks.	GSK2248761 200 mg Participants received GSK2248761 2 x 100 mg capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	Etravirine (ETV) Participants received ETV 2 x 100 mg tablet once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.
Overall Study STARTED	9	11	10
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	9	11	10

Reasons for withdrawal

Reasons for withdrawal
Measure	GSK2248761 100 Milligram (mg) Participants received GSK2248761 1 x 100 mg capsule once daily orally, 1 x Placebo to match GSK2248761 capsule once daily orally, Darunavir (DRV) 1 x 600 mg tablet twice daily with food orally, Ritonavir (RTV) 1 x 100 mg tablet twice daily orally and Raltegravir(RAL) 1 x 400 mg tablet twice daily orally up to 48 weeks.	GSK2248761 200 mg Participants received GSK2248761 2 x 100 mg capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	Etravirine (ETV) Participants received ETV 2 x 100 mg tablet once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.
Overall Study Adverse Event	0	1	0
Overall Study Study closed/terminated	7	9	7
Overall Study Lost to Follow-up	0	0	2
Overall Study Physician Decision	0	1	1
Overall Study Withdrawal by Subject	2	0	0

Baseline Characteristics

Dose-finding Study of GSK2248761 in Antiretroviral Therapy-experienced Subjects With NNRTI-resistant HIV Infection

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GSK2248761 100 mg n=9 Participants Participants received GSK2248761 1 x 100 mg capsule once daily orally, 1 x Placebo to match GSK2248761 capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	GSK2248761 200 mg n=11 Participants Participants received GSK2248761 2 x 100 mg capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	ETV 200 mg n=10 Participants Participants received ETV 2 x 100 mg tablet once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	Total n=30 Participants Total of all reporting groups
Age, Continuous	45.4 years STANDARD_DEVIATION 9.11 • n=5 Participants	42.4 years STANDARD_DEVIATION 11.60 • n=7 Participants	43.2 years STANDARD_DEVIATION 8.75 • n=5 Participants	43.6 years STANDARD_DEVIATION 9.74 • n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	9 Participants n=4 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	9 Participants n=7 Participants	5 Participants n=5 Participants	21 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	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 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	3 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	14 Participants n=4 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	14 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	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: At Week 16

Population: Intent-to-Treat-Exposed (ITT-E) consisted of all randomized participants who received at least one dose of investigational product (IP). Only those participants with data available at the indicated time point were analyzed.

Outcome measures

Outcome measures
Measure	GSK2248761 100 mg Participants received GSK2248761 1 x 100 mg capsule once daily orally, 1 x Placebo to match GSK2248761 capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	GSK2248761 200 mg Participants received GSK2248761 2 x 100 mg capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	ETV 200 mg n=3 Participants Participants received ETV 2 x 100 mg tablet once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.
Percentage of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies Per Milliliter (/mL) at Week 16	—	—	33 Percentage of participants

SECONDARY outcome

Timeframe: Up to follow-up i.e. 2-4 weeks after the last study visit (due to early termination the last visit was on 19 July 2011)

Population: Safety population consisted of all randomized participants who were exposed to IPs with the exception of any participant with documented evidence of not having consumed any amount of IP.

An AE was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.

Outcome measures

Outcome measures
Measure	GSK2248761 100 mg n=9 Participants Participants received GSK2248761 1 x 100 mg capsule once daily orally, 1 x Placebo to match GSK2248761 capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	GSK2248761 200 mg n=11 Participants Participants received GSK2248761 2 x 100 mg capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	ETV 200 mg n=10 Participants Participants received ETV 2 x 100 mg tablet once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.
Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AE	7 Participants	9 Participants	6 Participants
Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Any SAE	1 Participants	4 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to follow-up i.e. 2-4 weeks after the last study visit (due to early termination the last visit was on 19 July 2011)

Population: Safety population.

A toxicity was considered to be TE if it was greater than the Baseline grade, and if it had developed or increased post-Baseline in intensity (and prior to the last dose of IP). Division of acquired immunodeficiency syndrome (AIDS) toxicity scale for Grading the Severity of Adult and Pediatric Adverse Events Version 1.0 was used for grading i.e. Grade 3=severe and Grade 4=potentially life threatening. Categories with values have been presented. No toxicity-related dose reductions of IP was allowed. IP and background antiretroviral therapy (ART) was restarted as soon as medically appropriate; in general, this was no longer than 14\] days after discontinuation (unless Grade 3 or 4 toxicities persisted).

Outcome measures

Outcome measures
Measure	GSK2248761 100 mg n=9 Participants Participants received GSK2248761 1 x 100 mg capsule once daily orally, 1 x Placebo to match GSK2248761 capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	GSK2248761 200 mg n=11 Participants Participants received GSK2248761 2 x 100 mg capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	ETV 200 mg n=10 Participants Participants received ETV 2 x 100 mg tablet once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.
Number of Participants With Abnormal Clinical Chemistry Laboratory Data With Grade 3 or 4 Treatment-Emergent (TE) Toxicities Grade 3: Glucose	1 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Clinical Chemistry Laboratory Data With Grade 3 or 4 Treatment-Emergent (TE) Toxicities Grade 3: Hyperglycaemia	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to follow-up i.e. 2-4 weeks after the last study visit (due to early termination the last visit was on 19 July 2011)

Population: Safety population.

A toxicity was considered to be TE if it was greater than the Baseline grade, and if it had developed or increased post-Baseline in intensity (and prior to the last dose of IP). The hematology parameters included hemoglobin, total neutrophils, and white blood cells (WBC) count. Categories with values has been presented. Grade 3=severe and Grade 4=potentially life threatening. No toxicity-related dose reductions of IP was allowed. IP and background ART was restarted as soon as medically appropriate; in general, this was no longer than 14\] days after discontinuation (unless Grade 3 or 4 toxicities persisted).

Outcome measures

Outcome measures
Measure	GSK2248761 100 mg n=9 Participants Participants received GSK2248761 1 x 100 mg capsule once daily orally, 1 x Placebo to match GSK2248761 capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	GSK2248761 200 mg n=11 Participants Participants received GSK2248761 2 x 100 mg capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	ETV 200 mg n=10 Participants Participants received ETV 2 x 100 mg tablet once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.
Number of Participants With Abnormal Hematology Laboratory Data With Grade 3 or 4 TE Toxicities Grade 3: Total Neutrophils	1 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Hematology Laboratory Data With Grade 3 or 4 TE Toxicities Grade 3: WBC	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 2, 4, 8, 12 and 16

Population: ITT-E population. Only those participants available at the specified time points were analyzed.

A switch was defined as any ART substitution or addition in the participant's ART regimen. Any ART switch permitted per protocol that was determined necessary and documented prior to the first on-treatment visit where HIV-1 RNA was assessed could occur without penalty. However, any participants with an ART switch not permitted per protocol or ART switch permitted per protocol with a viral load \>=50 copies/mL at the time of the decision to switch was made was counted as a non-responder from that point onward for all assessment windows without a viral load measurement collected prior to the switch. Change from Baseline was calculated as (observed value - Baseline value). Baseline was Day 1. The unit is log10 copies per milliliter (log10 copies/mL).

Outcome measures

Outcome measures
Measure	GSK2248761 100 mg n=9 Participants Participants received GSK2248761 1 x 100 mg capsule once daily orally, 1 x Placebo to match GSK2248761 capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	GSK2248761 200 mg n=11 Participants Participants received GSK2248761 2 x 100 mg capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	ETV 200 mg n=10 Participants Participants received ETV 2 x 100 mg tablet once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.
Change From Baseline in Plasma HIV-1 RNA Prior to Switch of GSK2248761 Week 2	-1.845 Log10 copies/mL Standard Deviation 0.6029	-2.075 Log10 copies/mL Standard Deviation 0.7070	-1.730 Log10 copies/mL Standard Deviation 1.0923
Change From Baseline in Plasma HIV-1 RNA Prior to Switch of GSK2248761 Week 4	-1.985 Log10 copies/mL Standard Deviation 0.6818	-2.621 Log10 copies/mL Standard Deviation 0.5614	-2.064 Log10 copies/mL Standard Deviation 1.2401
Change From Baseline in Plasma HIV-1 RNA Prior to Switch of GSK2248761 Week 8	-2.332 Log10 copies/mL Standard Deviation 1.1915	-3.030 Log10 copies/mL Standard Deviation 0.1170	-1.850 Log10 copies/mL Standard Deviation 1.0895
Change From Baseline in Plasma HIV-1 RNA Prior to Switch of GSK2248761 Week 12	-1.997 Log10 copies/mL Standard Deviation 0.8918	-3.085 Log10 copies/mL Standard Deviation NA Not calculable for single participant	-1.678 Log10 copies/mL Standard Deviation 1.7096
Change From Baseline in Plasma HIV-1 RNA Prior to Switch of GSK2248761 Week 16	—	—	-0.820 Log10 copies/mL Standard Deviation 1.6424

SECONDARY outcome

Timeframe: Baseline (Day 1) and post switch Week 1, 2, 4, withdrawal and follow-up Week 4, 8, 12

Population: ITT-E. Only those participants available at the specified time points were analyzed.

Outcome measures

Outcome measures
Measure	GSK2248761 100 mg n=9 Participants Participants received GSK2248761 1 x 100 mg capsule once daily orally, 1 x Placebo to match GSK2248761 capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	GSK2248761 200 mg n=11 Participants Participants received GSK2248761 2 x 100 mg capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	ETV 200 mg Participants received ETV 2 x 100 mg tablet once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.
Change From Baseline in Plasma HIV-1 RNA After Switch of GSK2248761 Week 1 post switch	-2.080 log10 copies/mL Standard Deviation 1.2175	-2.197 log10 copies/mL Standard Deviation 1.0203	—
Change From Baseline in Plasma HIV-1 RNA After Switch of GSK2248761 Week 2 post switch	-2.376 log10 copies/mL Standard Deviation 1.1765	-2.229 log10 copies/mL Standard Deviation 1.2522	—
Change From Baseline in Plasma HIV-1 RNA After Switch of GSK2248761 Week 4 post switch	-1.617 log10 copies/mL Standard Deviation 0.8490	-2.545 log10 copies/mL Standard Deviation 0.6035	—
Change From Baseline in Plasma HIV-1 RNA After Switch of GSK2248761 Withdrawal	-2.070 log10 copies/mL Standard Deviation 1.4825	-1.978 log10 copies/mL Standard Deviation 1.5884	—
Change From Baseline in Plasma HIV-1 RNA After Switch of GSK2248761 4 Week follow-up	-2.123 log10 copies/mL Standard Deviation 1.2717	-1.999 log10 copies/mL Standard Deviation 1.2019	—
Change From Baseline in Plasma HIV-1 RNA After Switch of GSK2248761 8 Week follow-up	-2.101 log10 copies/mL Standard Deviation 1.3686	-1.251 log10 copies/mL Standard Deviation 1.3476	—
Change From Baseline in Plasma HIV-1 RNA After Switch of GSK2248761 12 Week follow-up	0.278 log10 copies/mL Standard Deviation NA Not calculable for 1 participant	-2.272 log10 copies/mL Standard Deviation 0.7077	—

SECONDARY outcome

Timeframe: Up to follow-up i.e. 2-4 weeks after the last study visit (due to early termination the last visit was on 19 July 2011)

Population: ITT-E population.

Clinical DP was defined as progression from Baseline HIV disease status:Category A at Baseline to Centers for Disease Control and Prevention(CDC) category B event, category A at Baseline to CDC category C event, category B at Baseline to CDC category C event, category C at Baseline to new CDC category C event or category A, B or C at Baseline to death. Category A consisted of one or more of the conditions like asymptomatic HIV infection, persistent generalized lymphadenopathy and acute (primary) HIV infection with accompanying illness in an adolescent or adult(\>13 years) with documented HIV infection. Category B consisted like Bacillary angiomatosis, Candidiasis, oropharyngeal (thrush), Candidiasis, vulvovaginal; persistent, frequent, oral, Herpes zoster etc. Category C included clinical conditions listed like Candidiasis of bronchi, trachea, or lungs, Candidiasis, esophageal, Cervical cancer, Coccidioidomycosis, disseminated or extrapulmonary etc in AIDS surveillance case definition.

Outcome measures

Outcome measures
Measure	GSK2248761 100 mg n=9 Participants Participants received GSK2248761 1 x 100 mg capsule once daily orally, 1 x Placebo to match GSK2248761 capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	GSK2248761 200 mg n=11 Participants Participants received GSK2248761 2 x 100 mg capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	ETV 200 mg n=10 Participants Participants received ETV 2 x 100 mg tablet once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.
Number of Participants Who Experienced Disease Progression (HIV-associated Conditions, AIDS and Death) Disease progression	0 Participants	0 Participants	0 Participants
Number of Participants Who Experienced Disease Progression (HIV-associated Conditions, AIDS and Death) Death	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and post switch Week 1, 2, 4, withdrawal and Follow-up Week 4, 8, 12

Population: ITT-E. Only those participants with data available at the specified time points were analyzed.

CD4 is a receptor for the HIV virus. Most of the damage to an AIDS participant's immune system was done by the virus' destruction of CD4+ lymphocytes. Absolute values of CD4+ cell counts after Switch of GSK2248761 has been presented.

Outcome measures

Outcome measures
Measure	GSK2248761 100 mg n=9 Participants Participants received GSK2248761 1 x 100 mg capsule once daily orally, 1 x Placebo to match GSK2248761 capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	GSK2248761 200 mg n=11 Participants Participants received GSK2248761 2 x 100 mg capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	ETV 200 mg Participants received ETV 2 x 100 mg tablet once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.
Absolute Values of CD4+ Cell Counts After Switch of GSK2248761 Baseline	229.2 Cells per cubic millimeter (cells/mm^3) Standard Deviation 131.99	162.5 Cells per cubic millimeter (cells/mm^3) Standard Deviation 108.16	—
Absolute Values of CD4+ Cell Counts After Switch of GSK2248761 Baseline switch	311.0 Cells per cubic millimeter (cells/mm^3) Standard Deviation 95.11	164.3 Cells per cubic millimeter (cells/mm^3) Standard Deviation 107.79	—
Absolute Values of CD4+ Cell Counts After Switch of GSK2248761 Week 1 post switch	253.0 Cells per cubic millimeter (cells/mm^3) Standard Deviation 122.25	189.9 Cells per cubic millimeter (cells/mm^3) Standard Deviation 132.13	—
Absolute Values of CD4+ Cell Counts After Switch of GSK2248761 Week 2 post switch	263.7 Cells per cubic millimeter (cells/mm^3) Standard Deviation 112.85	179.0 Cells per cubic millimeter (cells/mm^3) Standard Deviation 101.59	—
Absolute Values of CD4+ Cell Counts After Switch of GSK2248761 Week 4 post switch	471.5 Cells per cubic millimeter (cells/mm^3) Standard Deviation 64.35	199.6 Cells per cubic millimeter (cells/mm^3) Standard Deviation 48.72	—
Absolute Values of CD4+ Cell Counts After Switch of GSK2248761 Withdrawal	254.6 Cells per cubic millimeter (cells/mm^3) Standard Deviation 137.11	188.5 Cells per cubic millimeter (cells/mm^3) Standard Deviation 95.30	—
Absolute Values of CD4+ Cell Counts After Switch of GSK2248761 Week 4 follow-up	289.0 Cells per cubic millimeter (cells/mm^3) Standard Deviation 154.44	237.9 Cells per cubic millimeter (cells/mm^3) Standard Deviation 110.27	—
Absolute Values of CD4+ Cell Counts After Switch of GSK2248761 Week 8 follow-up	277.5 Cells per cubic millimeter (cells/mm^3) Standard Deviation 139.41	207.2 Cells per cubic millimeter (cells/mm^3) Standard Deviation 117.79	—
Absolute Values of CD4+ Cell Counts After Switch of GSK2248761 Week 12 follow-up	—	329.3 Cells per cubic millimeter (cells/mm^3) Standard Deviation 159.20	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 2, 4, 8, 12 and 16

Population: ITT-E. Only those participants available at the specified time points were analyzed.

CD4 is a receptor for the HIV virus. Most of the damage to an AIDS patient's immune system is done by the virus' destruction of CD4+ lymphocytes. Change from Baseline was calculated as (observed value - Baseline value). Baseline was Day 1 value.

Outcome measures

Outcome measures
Measure	GSK2248761 100 mg n=9 Participants Participants received GSK2248761 1 x 100 mg capsule once daily orally, 1 x Placebo to match GSK2248761 capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	GSK2248761 200 mg n=11 Participants Participants received GSK2248761 2 x 100 mg capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	ETV 200 mg n=10 Participants Participants received ETV 2 x 100 mg tablet once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.
Change From Baseline in CD4+ Cell Counts Prior to Switch of GSK2248761 Week 2	43.0 Cells/mm^3 Standard Deviation 65.74	21.2 Cells/mm^3 Standard Deviation 58.05	62.2 Cells/mm^3 Standard Deviation 81.88
Change From Baseline in CD4+ Cell Counts Prior to Switch of GSK2248761 Week 4	122.8 Cells/mm^3 Standard Deviation 133.34	60.7 Cells/mm^3 Standard Deviation 79.66	81.4 Cells/mm^3 Standard Deviation 96.88
Change From Baseline in CD4+ Cell Counts Prior to Switch of GSK2248761 Week 8	76.4 Cells/mm^3 Standard Deviation 111.61	57.3 Cells/mm^3 Standard Deviation 54.29	71.0 Cells/mm^3 Standard Deviation 61.19
Change From Baseline in CD4+ Cell Counts Prior to Switch of GSK2248761 Week 12	41.0 Cells/mm^3 Standard Deviation 21.21	30.0 Cells/mm^3 Standard Deviation NA Not calculable for 1 participant	61.5 Cells/mm^3 Standard Deviation 91.53
Change From Baseline in CD4+ Cell Counts Prior to Switch of GSK2248761 Week 16	—	—	-7.0 Cells/mm^3 Standard Deviation 2.00

SECONDARY outcome

Timeframe: Baseline (Day 1) and post switch Week 1, 2, 4, withdrawal and Follow-up Week 4, 8, 12

Population: ITT-E. Only those participants available at the specified time points were analyzed.

Outcome measures

Outcome measures
Measure	GSK2248761 100 mg n=9 Participants Participants received GSK2248761 1 x 100 mg capsule once daily orally, 1 x Placebo to match GSK2248761 capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	GSK2248761 200 mg n=11 Participants Participants received GSK2248761 2 x 100 mg capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	ETV 200 mg Participants received ETV 2 x 100 mg tablet once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.
Change From Baseline in CD4+ Cell Counts After Switch of GSK2248761 Week 1 post switch	48.2 Cells/mm^3 Standard Deviation 61.10	7.4 Cells/mm^3 Standard Deviation 54.99	—
Change From Baseline in CD4+ Cell Counts After Switch of GSK2248761 Week 2 post switch	58.8 Cells/mm^3 Standard Deviation 48.55	4.3 Cells/mm^3 Standard Deviation 42.28	—
Change From Baseline in CD4+ Cell Counts After Switch of GSK2248761 Week 4 post switch	74.0 Cells/mm^3 Standard Deviation 62.23	16.6 Cells/mm^3 Standard Deviation 61.59	—
Change From Baseline in CD4+ Cell Counts After Switch of GSK2248761 Withdrawal	44.1 Cells/mm^3 Standard Deviation 74.26	26.0 Cells/mm^3 Standard Deviation 71.00	—
Change From Baseline in CD4+ Cell Counts After Switch of GSK2248761 4 Week follow-up	59.8 Cells/mm^3 Standard Deviation 56.62	72.0 Cells/mm^3 Standard Deviation 102.38	—
Change From Baseline in CD4+ Cell Counts After Switch of GSK2248761 8 Week follow-up	66.3 Cells/mm^3 Standard Deviation 54.09	32.3 Cells/mm^3 Standard Deviation 34.16	—
Change From Baseline in CD4+ Cell Counts After Switch of GSK2248761 12 Week follow-up	—	113.7 Cells/mm^3 Standard Deviation 63.61	—

SECONDARY outcome

Timeframe: Up to follow-up i.e. 2-4 weeks after the last study visit (due to early termination the last visit was on 19 July 2011)

Population: Safety population.

An AE is defined as 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.

Outcome measures

Outcome measures
Measure	GSK2248761 100 mg n=9 Participants Participants received GSK2248761 1 x 100 mg capsule once daily orally, 1 x Placebo to match GSK2248761 capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	GSK2248761 200 mg n=11 Participants Participants received GSK2248761 2 x 100 mg capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	ETV 200 mg n=10 Participants Participants received ETV 2 x 100 mg tablet once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.
Number of Participants Who Discontinued Treatment Due to AEs	0 Participants	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to follow-up i.e. 2-4 weeks after the last study visit (due to early termination the last visit was on 19 July 2011)

Population: Safety population.

Number of participants with ECG of PCI above 480 has been presented. ECG was be performed twice on Day 1 at least 5 minutes apart and following 5 minutes of rest in a semi supine position at ∼1 hour prior to first dose. ECG evaluations at other visits was obtained after dosing, preferably at 2 hours post dosing. An ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and corrected QT (QTc) intervals was used.

Outcome measures

Outcome measures
Measure	GSK2248761 100 mg n=9 Participants Participants received GSK2248761 1 x 100 mg capsule once daily orally, 1 x Placebo to match GSK2248761 capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	GSK2248761 200 mg n=11 Participants Participants received GSK2248761 2 x 100 mg capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	ETV 200 mg n=10 Participants Participants received ETV 2 x 100 mg tablet once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.
Number of Participants With Electrocardiograph (ECG) With Values of Potential Critical Concern (PCI)	0 Participants	0 Participants	0 Participants

Adverse Events

GSK2248761 100 mg

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

GSK2248761 200 mg

Serious events: 4 serious events

Other events: 9 other events

Deaths: 0 deaths

ETV 200 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	GSK2248761 100 mg n=9 participants at risk Participants received GSK2248761 1 x 100 mg capsule once daily orally, 1 x Placebo to match GSK2248761 capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	GSK2248761 200 mg n=11 participants at risk Participants received GSK2248761 2 x 100 mg capsule once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.	ETV 200 mg n=10 participants at risk Participants received ETV 2 x 100 mg tablet once daily orally, DRV 1 x 600 mg tablet twice daily with food orally, RTV 1 x 100 mg tablet twice daily orally and RAL 1 x 400 mg tablet twice daily orally up to 48 weeks.
Nervous system disorders Convulsion	0.00% 0/9 • Up to follow-up i.e. 2-4 weeks after the last study visit (due to early termination the last visit was on 19 July 2011) Safety population was used for the analysis.	36.4% 4/11 • Up to follow-up i.e. 2-4 weeks after the last study visit (due to early termination the last visit was on 19 July 2011) Safety population was used for the analysis.	0.00% 0/10 • Up to follow-up i.e. 2-4 weeks after the last study visit (due to early termination the last visit was on 19 July 2011) Safety population was used for the analysis.
Injury, poisoning and procedural complications Facial bones fracture	11.1% 1/9 • Up to follow-up i.e. 2-4 weeks after the last study visit (due to early termination the last visit was on 19 July 2011) Safety population was used for the analysis.	0.00% 0/11 • Up to follow-up i.e. 2-4 weeks after the last study visit (due to early termination the last visit was on 19 July 2011) Safety population was used for the analysis.	0.00% 0/10 • Up to follow-up i.e. 2-4 weeks after the last study visit (due to early termination the last visit was on 19 July 2011) Safety population was used for the analysis.
Psychiatric disorders Schizophrenia	0.00% 0/9 • Up to follow-up i.e. 2-4 weeks after the last study visit (due to early termination the last visit was on 19 July 2011) Safety population was used for the analysis.	9.1% 1/11 • Up to follow-up i.e. 2-4 weeks after the last study visit (due to early termination the last visit was on 19 July 2011) Safety population was used for the analysis.	0.00% 0/10 • Up to follow-up i.e. 2-4 weeks after the last study visit (due to early termination the last visit was on 19 July 2011) Safety population was used for the analysis.

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