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

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ClinicalTrials.gov Identifier: NCT01199731
Recruitment Status : Terminated (The study was stopped due to safety concerns)
First Posted : September 13, 2010
Results First Posted : October 12, 2017
Last Update Posted : November 17, 2017
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Infection, Human Immunodeficiency Virus
Interventions Drug: GSK2248761 100 mg once daily
Drug: GSK2248761 200 mg once daily
Drug: Etravirine
Enrollment 30
Recruitment Details 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.
Pre-assignment Details 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.
Arm/Group Title GSK2248761 100 Milligram (mg) GSK2248761 200 mg Etravirine (ETV)
Hide Arm/Group Description 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. 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. 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.
Period Title: Overall Study
Started 9 11 10
Completed 0 0 0
Not Completed 9 11 10
Reason Not Completed
Adverse Event             0             1             0
Study closed/terminated             7             9             7
Lost to Follow-up             0             0             2
Physician Decision             0             1             1
Withdrawal by Subject             2             0             0
Arm/Group Title GSK2248761 100 mg GSK2248761 200 mg ETV 200 mg Total
Hide Arm/Group Description 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. 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. 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 of all reporting groups
Overall Number of Baseline Participants 9 11 10 30
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 9 participants 11 participants 10 participants 30 participants
45.4  (9.11) 42.4  (11.60) 43.2  (8.75) 43.6  (9.74)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 11 participants 10 participants 30 participants
Female
2
  22.2%
2
  18.2%
5
  50.0%
9
  30.0%
Male
7
  77.8%
9
  81.8%
5
  50.0%
21
  70.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 11 participants 10 participants 30 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
  11.1%
0
   0.0%
0
   0.0%
1
   3.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
  33.3%
5
  45.5%
6
  60.0%
14
  46.7%
White
5
  55.6%
5
  45.5%
4
  40.0%
14
  46.7%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
1
   9.1%
0
   0.0%
1
   3.3%
1.Primary Outcome
Title Percentage of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies Per Milliliter (/mL) at Week 16
Hide Description 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.
Time Frame At Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title GSK2248761 100 mg GSK2248761 200 mg ETV 200 mg
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 0 0 3
Measure Type: Number
Unit of Measure: Percentage of participants
33
2.Secondary Outcome
Title Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title GSK2248761 100 mg GSK2248761 200 mg ETV 200 mg
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 9 11 10
Measure Type: Count of Participants
Unit of Measure: Participants
Any AE
7
  77.8%
9
  81.8%
6
  60.0%
Any SAE
1
  11.1%
4
  36.4%
0
   0.0%
3.Secondary Outcome
Title Number of Participants With Abnormal Clinical Chemistry Laboratory Data With Grade 3 or 4 Treatment-Emergent (TE) Toxicities
Hide Description 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).
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title GSK2248761 100 mg GSK2248761 200 mg ETV 200 mg
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 9 11 10
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 3: Glucose
1
  11.1%
0
   0.0%
0
   0.0%
Grade 3: Hyperglycaemia
1
  11.1%
0
   0.0%
0
   0.0%
4.Secondary Outcome
Title Number of Participants With Abnormal Hematology Laboratory Data With Grade 3 or 4 TE Toxicities
Hide Description 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).
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title GSK2248761 100 mg GSK2248761 200 mg ETV 200 mg
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 9 11 10
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 3: Total Neutrophils
1
  11.1%
1
   9.1%
0
   0.0%
Grade 3: WBC
0
   0.0%
1
   9.1%
0
   0.0%
5.Secondary Outcome
Title Change From Baseline in Plasma HIV-1 RNA Prior to Switch of GSK2248761
Hide Description 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).
Time Frame Baseline (Day 1) and Week 2, 4, 8, 12 and 16
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E population. Only those participants available at the specified time points were analyzed.
Arm/Group Title GSK2248761 100 mg GSK2248761 200 mg ETV 200 mg
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 9 11 10
Mean (Standard Deviation)
Unit of Measure: Log10 copies/mL
Week 2 Number Analyzed 8 participants 10 participants 9 participants
-1.845  (0.6029) -2.075  (0.7070) -1.730  (1.0923)
Week 4 Number Analyzed 4 participants 6 participants 9 participants
-1.985  (0.6818) -2.621  (0.5614) -2.064  (1.2401)
Week 8 Number Analyzed 5 participants 4 participants 9 participants
-2.332  (1.1915) -3.030  (0.1170) -1.850  (1.0895)
Week 12 Number Analyzed 3 participants 1 participants 7 participants
-1.997  (0.8918) -3.085 [1]   (NA) -1.678  (1.7096)
Week 16 Number Analyzed 0 participants 0 participants 3 participants
-0.820  (1.6424)
[1]
Not calculable for single participant
6.Secondary Outcome
Title Change From Baseline in Plasma HIV-1 RNA After Switch of GSK2248761
Hide Description 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.
Time Frame Baseline (Day 1) and post switch Week 1, 2, 4, withdrawal and follow-up Week 4, 8, 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E. Only those participants available at the specified time points were analyzed.
Arm/Group Title GSK2248761 100 mg GSK2248761 200 mg
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 9 11
Mean (Standard Deviation)
Unit of Measure: log10 copies/mL
Week 1 post switch Number Analyzed 6 participants 8 participants
-2.080  (1.2175) -2.197  (1.0203)
Week 2 post switch Number Analyzed 6 participants 7 participants
-2.376  (1.1765) -2.229  (1.2522)
Week 4 post switch Number Analyzed 2 participants 5 participants
-1.617  (0.8490) -2.545  (0.6035)
Withdrawal Number Analyzed 7 participants 11 participants
-2.070  (1.4825) -1.978  (1.5884)
4 Week follow-up Number Analyzed 9 participants 10 participants
-2.123  (1.2717) -1.999  (1.2019)
8 Week follow-up Number Analyzed 8 participants 9 participants
-2.101  (1.3686) -1.251  (1.3476)
12 Week follow-up Number Analyzed 1 participants 3 participants
0.278 [1]   (NA) -2.272  (0.7077)
[1]
Not calculable for 1 participant
7.Secondary Outcome
Title Number of Participants Who Experienced Disease Progression (HIV-associated Conditions, AIDS and Death)
Hide Description 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E population.
Arm/Group Title GSK2248761 100 mg GSK2248761 200 mg ETV 200 mg
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 9 11 10
Measure Type: Count of Participants
Unit of Measure: Participants
Disease progression
0
   0.0%
0
   0.0%
0
   0.0%
Death
0
   0.0%
0
   0.0%
0
   0.0%
8.Secondary Outcome
Title Absolute Values of CD4+ Cell Counts After Switch of GSK2248761
Hide Description 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.
Time Frame Baseline (Day 1) and post switch Week 1, 2, 4, withdrawal and Follow-up Week 4, 8, 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title GSK2248761 100 mg GSK2248761 200 mg
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 9 11
Mean (Standard Deviation)
Unit of Measure: Cells per cubic millimeter (cells/mm^3)
Baseline Number Analyzed 9 participants 11 participants
229.2  (131.99) 162.5  (108.16)
Baseline switch Number Analyzed 4 participants 6 participants
311.0  (95.11) 164.3  (107.79)
Week 1 post switch Number Analyzed 6 participants 7 participants
253.0  (122.25) 189.9  (132.13)
Week 2 post switch Number Analyzed 6 participants 8 participants
263.7  (112.85) 179.0  (101.59)
Week 4 post switch Number Analyzed 2 participants 5 participants
471.5  (64.35) 199.6  (48.72)
Withdrawal Number Analyzed 7 participants 11 participants
254.6  (137.11) 188.5  (95.30)
Week 4 follow-up Number Analyzed 9 participants 10 participants
289.0  (154.44) 237.9  (110.27)
Week 8 follow-up Number Analyzed 8 participants 10 participants
277.5  (139.41) 207.2  (117.79)
Week 12 follow-up Number Analyzed 0 participants 3 participants
329.3  (159.20)
9.Secondary Outcome
Title Change From Baseline in CD4+ Cell Counts Prior to Switch of GSK2248761
Hide Description 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.
Time Frame Baseline (Day 1) and Week 2, 4, 8, 12 and 16
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E. Only those participants available at the specified time points were analyzed.
Arm/Group Title GSK2248761 100 mg GSK2248761 200 mg ETV 200 mg
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 9 11 10
Mean (Standard Deviation)
Unit of Measure: Cells/mm^3
Week 2 Number Analyzed 8 participants 10 participants 9 participants
43.0  (65.74) 21.2  (58.05) 62.2  (81.88)
Week 4 Number Analyzed 4 participants 6 participants 9 participants
122.8  (133.34) 60.7  (79.66) 81.4  (96.88)
Week 8 Number Analyzed 5 participants 4 participants 9 participants
76.4  (111.61) 57.3  (54.29) 71.0  (61.19)
Week 12 Number Analyzed 2 participants 1 participants 6 participants
41.0  (21.21) 30.0 [1]   (NA) 61.5  (91.53)
Week 16 Number Analyzed 0 participants 0 participants 3 participants
-7.0  (2.00)
[1]
Not calculable for 1 participant
10.Secondary Outcome
Title Change From Baseline in CD4+ Cell Counts After Switch of GSK2248761
Hide Description 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.
Time Frame Baseline (Day 1) and post switch Week 1, 2, 4, withdrawal and Follow-up Week 4, 8, 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E. Only those participants available at the specified time points were analyzed.
Arm/Group Title GSK2248761 100 mg GSK2248761 200 mg
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 9 11
Mean (Standard Deviation)
Unit of Measure: Cells/mm^3
Week 1 post switch Number Analyzed 6 participants 7 participants
48.2  (61.10) 7.4  (54.99)
Week 2 post switch Number Analyzed 6 participants 8 participants
58.8  (48.55) 4.3  (42.28)
Week 4 post switch Number Analyzed 2 participants 5 participants
74.0  (62.23) 16.6  (61.59)
Withdrawal Number Analyzed 7 participants 11 participants
44.1  (74.26) 26.0  (71.00)
4 Week follow-up Number Analyzed 9 participants 10 participants
59.8  (56.62) 72.0  (102.38)
8 Week follow-up Number Analyzed 8 participants 10 participants
66.3  (54.09) 32.3  (34.16)
12 Week follow-up Number Analyzed 0 participants 3 participants
113.7  (63.61)
11.Secondary Outcome
Title Number of Participants Who Discontinued Treatment Due to AEs
Hide Description 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title GSK2248761 100 mg GSK2248761 200 mg ETV 200 mg
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 9 11 10
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
2
  18.2%
0
   0.0%
12.Secondary Outcome
Title Number of Participants With Electrocardiograph (ECG) With Values of Potential Critical Concern (PCI)
Hide Description 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title GSK2248761 100 mg GSK2248761 200 mg ETV 200 mg
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 9 11 10
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
Time Frame 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)
Adverse Event Reporting Description Safety population was used for the analysis.
 
Arm/Group Title GSK2248761 100 mg GSK2248761 200 mg ETV 200 mg
Hide Arm/Group Description 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. 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. 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.
All-Cause Mortality
GSK2248761 100 mg GSK2248761 200 mg ETV 200 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/9 (0.00%)   0/11 (0.00%)   0/10 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
GSK2248761 100 mg GSK2248761 200 mg ETV 200 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/9 (11.11%)   4/11 (36.36%)   0/10 (0.00%) 
Injury, poisoning and procedural complications       
Facial bones fracture  1  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%) 
Nervous system disorders       
Convulsion  1  0/9 (0.00%)  4/11 (36.36%)  0/10 (0.00%) 
Psychiatric disorders       
Schizophrenia  1  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%) 
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
GSK2248761 100 mg GSK2248761 200 mg ETV 200 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/9 (88.89%)   9/11 (81.82%)   6/10 (60.00%) 
Cardiac disorders       
Sinus bradycardia  1  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%) 
Ear and labyrinth disorders       
Cerumen impaction  1  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%) 
Ear pain  1  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%) 
Tinnitus  1  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%) 
Eye disorders       
Vision blurred  1  1/9 (11.11%)  1/11 (9.09%)  0/10 (0.00%) 
Gastrointestinal disorders       
Diarrhoea  1  2/9 (22.22%)  3/11 (27.27%)  2/10 (20.00%) 
Constipation  1  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%) 
Dyspepsia  1  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%) 
Dysphagia  1  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%) 
Nausea  1  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%) 
Paraesthesia oral  1  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%) 
General disorders       
Fatigue  1  1/9 (11.11%)  1/11 (9.09%)  0/10 (0.00%) 
Chest pain  1  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%) 
Malaise  1  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%) 
Oedema peripheral  1  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%) 
Hepatobiliary disorders       
Hyperbilirubinaemia  1  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%) 
Infections and infestations       
Sinusitis  1  3/9 (33.33%)  0/11 (0.00%)  0/10 (0.00%) 
Acute sinusitis  1  0/9 (0.00%)  1/11 (9.09%)  1/10 (10.00%) 
Influenza  1  1/9 (11.11%)  0/11 (0.00%)  1/10 (10.00%) 
Body tinea  1  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%) 
Bronchitis  1  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%) 
Candidiasis  1  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%) 
Carbuncle  1  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%) 
Gastroenteritis  1  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%) 
Pharyngitis  1  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%) 
Pharyngitis streptococcal  1  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%) 
Sepsis  1  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%) 
Upper respiratory tract infection  1  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%) 
Urinary tract infection  1  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%) 
Vaginal infection  1  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%) 
Injury, poisoning and procedural complications       
Concussion  1  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%) 
Fall  1  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%) 
Laceration  1  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%) 
Investigations       
Blood creatine phosphokinase increased  1  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%) 
Metabolism and nutrition disorders       
Decreased appetite  1  1/9 (11.11%)  0/11 (0.00%)  1/10 (10.00%) 
Hypokalaemia  1  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  1/9 (11.11%)  0/11 (0.00%)  1/10 (10.00%) 
Muscular weakness  1  2/9 (22.22%)  0/11 (0.00%)  0/10 (0.00%) 
Musculoskeletal pain  1  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%) 
Rhabdomyolysis  1  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%) 
Nervous system disorders       
Headache  1  1/9 (11.11%)  1/11 (9.09%)  1/10 (10.00%) 
Dizziness  1  1/9 (11.11%)  1/11 (9.09%)  0/10 (0.00%) 
Syncope  1  1/9 (11.11%)  1/11 (9.09%)  0/10 (0.00%) 
Amnesia  1  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%) 
Carpal tunnel syndrome  1  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%) 
Convulsion  1  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%) 
Disturbance in attention  1  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%) 
Dysgeusia  1  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%) 
Paraesthesia  1  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%) 
Parkinsonism  1  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%) 
Petit mal epilepsy  1  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%) 
Somnolence  1  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%) 
Psychiatric disorders       
Insomnia  1  3/9 (33.33%)  0/11 (0.00%)  0/10 (0.00%) 
Anxiety disorder  1  2/9 (22.22%)  0/11 (0.00%)  0/10 (0.00%) 
Depression  1  1/9 (11.11%)  1/11 (9.09%)  0/10 (0.00%) 
Abnormal dreams  1  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%) 
Anxiety  1  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%) 
Renal and urinary disorders       
Dysuria  1  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%) 
Pollakiuria  1  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%) 
Reproductive system and breast disorders       
Sexual dysfunction  1  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  0/9 (0.00%)  2/11 (18.18%)  0/10 (0.00%) 
Dyspnoea  1  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%) 
Nasal congestion  1  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%) 
Rhinitis allergic  1  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%) 
Skin and subcutaneous tissue disorders       
Pruritus  1  1/9 (11.11%)  1/11 (9.09%)  0/10 (0.00%) 
Eosinophilic pustular folliculitis  1  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%) 
Night sweats  1  1/9 (11.11%)  0/11 (0.00%)  0/10 (0.00%) 
Photosensitivity reaction  1  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%) 
Rash  1  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%) 
Vascular disorders       
Deep vein thrombosis  1  0/9 (0.00%)  1/11 (9.09%)  0/10 (0.00%) 
Hypertension  1  0/9 (0.00%)  0/11 (0.00%)  1/10 (10.00%) 
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
Enrollment in this study was terminated prematurely on 01 April 2011 due to a safety finding (convulsion) in 5/20 participants receiving GSK2248761.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: ViiV Healthcare
Phone: 866-435-7343
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Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT01199731     History of Changes
Other Study ID Numbers: 113399
First Submitted: September 9, 2010
First Posted: September 13, 2010
Results First Submitted: August 17, 2017
Results First Posted: October 12, 2017
Last Update Posted: November 17, 2017