ClinicalTrials.gov
ClinicalTrials.gov Menu

Study Of Chemokine Coreceptor 5 (CCR5) Antagonist GW873140 In R5-Tropic Treatment-Experienced HIV-Infected Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00197145
Recruitment Status : Terminated
First Posted : September 20, 2005
Results First Posted : November 2, 2018
Last Update Posted : November 2, 2018
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Primary Purpose: Treatment
Condition Infection, Human Immunodeficiency Virus I
Intervention Drug: GW873140
Enrollment 24
Recruitment Details The study was planned on 406 male or female participants infected with Human immunodeficiency type 1 (HIV-1) virus, aged 18 years or older, across 15 centres in the United States and at 1 site in Canada from 21 July 2005 to 11 September 2007. Study was early terminated prior to the completion of enrollment.
Pre-assignment Details A total of 24 participants comprised All Randomized Subject Population who were randomized in a ratio of 1:1 to GW873140 (aplaviroc [APL])+optimized background therapy (OBT) and placebo+OBT. Intent-to Treat (ITT) Population was n=24, used for all analysis.
Arm/Group Title APL + OBT Placebo + OBT
Hide Arm/Group Description Participants were administered APL tablets orally as 400 milligram (mg) twice daily (BID) for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was ritonavir (RTV)- boosted protease inhibitor (PI). Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. Fixed dose combination tablets (FDC) was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (lopinavir [LPV]/RTV) was counted as one drug. Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was ritonavir (RTV)- boosted protease inhibitor (PI). Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. Fixed dose combination tablets (FDC) was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (lopinavir [LPV]/RTV) was counted as one drug.
Period Title: Period 1: Randomized Treatment Phase
Started 13 11
Completed 0 0
Not Completed 13 11
Reason Not Completed
Withdrawal by Subject             1             1
Sponsor terminated study             10             8
Other             2             2
Period Title: Period 2 : Open Label Phase
Started 10 0
Completed 0 0
Not Completed 10 0
Reason Not Completed
Insufficient viral load response             1             0
Protocol defined virological failure             3             0
Availability of alternative ART             2             0
Were ongoing till data freeze             3             0
Other             1             0
Arm/Group Title APL + OBT Placebo + OBT Total
Hide Arm/Group Description Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug. Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug. Total of all reporting groups
Overall Number of Baseline Participants 13 11 24
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 13 participants 11 participants 24 participants
46.8  (7.03) 44.5  (5.68) 45.8  (6.42)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 11 participants 24 participants
Female
2
  15.4%
2
  18.2%
4
  16.7%
Male
11
  84.6%
9
  81.8%
20
  83.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 11 participants 24 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
  23.1%
3
  27.3%
6
  25.0%
White
10
  76.9%
8
  72.7%
18
  75.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Number of Participants With Plasma HIV-1 RNA <400 Copies Per Milliliter (Copies /mL) at Week 24 and 48
Hide Description Assessment for plasma HIV-1 RNA was done at Week 24 and also planned at Week 48 by polymerase chain reaction (PCR) analysis. Data is reported for number of participants with plasma HIV-1 RNA <400 copies/mL at Week 24. Data was not collected for Week 48 due to early termination of the study.
Time Frame Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) Population comprised of all participants randomized with evidence of receiving at least one dose of study medication. The analysis was an observed analysis and only participants with data available at the indicated timepoints were included.
Arm/Group Title APL + OBT Placebo + OBT
Hide Arm/Group Description:
Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 7 0
Measure Type: Count of Participants
Unit of Measure: Participants
5
  71.4%
0
2.Primary Outcome
Title Average Area Under the Curve Minus Baseline (AAUCMB) of Plasma HIV-1 RNA Through the Entire Study Period
Hide Description The area under the plasma HIV-1 RNA curve (AUC) was computed using the trapezoidal rule for all assessments (scheduled and unscheduled) at their actual time points. Baseline was defined as the mean of the Baseline (Day 1) and pre-treatment visit values. Participants without a Baseline assessment was removed from the analysis. The AAUCMB was computed by the AUC divided by the duration of the profile (i.e., the number of days on randomized therapy) minus the Baseline measurement. Data is reported up to Week 40 only due to early termination of the study.
Time Frame Up to Week 40
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title APL + OBT Placebo + OBT
Hide Arm/Group Description:
Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 11 7
Mean (Standard Deviation)
Unit of Measure: Log10 copies/mL
-2.03  (0.990) -1.14  (0.766)
3.Primary Outcome
Title Number of Participants With >= 1.0 log10 Copies/mL Decrease in Plasma HIV-1 RNA From Baseline Over Time
Hide Description The plasma HIV-1 RNA polymerase chain reaction (PCR) assessments were planned at pre-Baseline (between 1 and 14 days prior to Day 1), up to Week 12 Follow- up of the Randomized Phase, up to Week 12 Follow-up of the Open Labeled Non-Randomized phase and every 6 months Follow-up of off study drug/on study phase, however the study was early terminated at Week 40. Baseline was defined as the mean of the Baseline (Day 1) and pre-treatment visit values.
Time Frame Day 1 up to Week 12 Follow-up of the Randomized Treatment phase, up to Week 12 Follow-up of the Open Labeled Non-Randomized phase and every 6 months Follow-up of off study drug/on study phase
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Data were not collected for this outcome measure due to early termination of the study.
Arm/Group Title APL + OBT Placebo + OBT
Hide Arm/Group Description:
Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Number of Participants With Plasma HIV-1 RNA <50 Copies/mL at Week 24 and 48
Hide Description Assessment for plasma HIV-1 RNA was done at Week 24 and also planned at Week 48 by PCR analysis. Data is reported for number of participants with plasma HIV-1 RNA <50 copies/mL at Week 24. Data was not collected for Week 48 due to early termination of the study.
Time Frame Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. The analysis was an observed analysis and only participants with data available at the indicated timepoints were included.
Arm/Group Title APL + OBT Placebo + OBT
Hide Arm/Group Description:
Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 7 0
Measure Type: Count of Participants
Unit of Measure: Participants
5
  71.4%
0
5.Secondary Outcome
Title Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE), Death, Drug-related AE and AE Leading to Treatment Discontinuation
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 SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, hypersensitivity reaction to abacavir. AEs were classified as potentially drug-related, based on the investigator's judgment.
Time Frame Up to Follow-up (Week 52)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title APL + OBT Placebo + OBT
Hide Arm/Group Description:
Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 13 11
Measure Type: Count of Participants
Unit of Measure: Participants
Any AE
11
  84.6%
5
  45.5%
Any SAE
0
   0.0%
0
   0.0%
Any Death
0
   0.0%
0
   0.0%
Drug-related AE
7
  53.8%
2
  18.2%
Any AE Leading to Treatment Discontinuation
0
   0.0%
0
   0.0%
6.Secondary Outcome
Title Number of Participants With Treatment Emergent Laboratory Abnormalities for Chemistry Data at Any Visit Post-Baseline
Hide Description The participants with treatment emergent toxicities of laboratory abnormalities for chemistry data is reported . Participants with toxicities were categorized according to the division of AIDS (DAIDS) toxicity grading scale. Scale ranges from grade 1(mild)=symptoms causing no or minimal interference with usual social & functional activities, grade 2 (moderate)=symptoms causing greater than minimal interference with usual social & functional activities, grade 3 (severe)=symptoms causing inability to perform usual social & functional activities and grade 4 (potentially life threatening)=symptoms causing inability to perform basic self-care functions or medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death. Scale ranges from 1-4, where higher grade reflects greater severity of symptoms. Baseline was defined as assessments done at Day 1. Only those parameters for which at least one value of toxicity grade was reported are summarized.
Time Frame Up to Week 40
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title APL + OBT Placebo + OBT
Hide Arm/Group Description:
Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 13 11
Measure Type: Count of Participants
Unit of Measure: Participants
Alanine Amino Transferase (ALT), Grade 1
0
   0.0%
1
   9.1%
ALT, Grade 2
1
   7.7%
0
   0.0%
Albumin, Grade 2
1
   7.7%
0
   0.0%
Alkaline Phosphatase (ALP), Grade 1
2
  15.4%
3
  27.3%
Aspartate Amino Transferase (AST), Grade 1
1
   7.7%
2
  18.2%
AST, Grade 2
1
   7.7%
0
   0.0%
Carbon Dioxide content/Bicarbonate (CO2), Grade 1
2
  15.4%
3
  27.3%
Cholesterol, Grade 1
0
   0.0%
1
   9.1%
Cholesterol, Grade 2
1
   7.7%
0
   0.0%
Creatine Kinase (CK), Grade 1
0
   0.0%
1
   9.1%
CK, Grade 2
1
   7.7%
0
   0.0%
CK, Grade 3
2
  15.4%
0
   0.0%
Creatinine, Grade 1
1
   7.7%
2
  18.2%
Glucose, Grade 1
3
  23.1%
3
  27.3%
Glucose, Grade 2
3
  23.1%
2
  18.2%
Glucose, Grade 3
1
   7.7%
0
   0.0%
Low Density lipoprotein (LDL) Cholesterol, Grade 2
1
   7.7%
0
   0.0%
Lipase, Grade 1
3
  23.1%
0
   0.0%
Lipase, Grade 2
1
   7.7%
0
   0.0%
Potassium, Grade 4
0
   0.0%
1
   9.1%
Sodium, Grade 1
3
  23.1%
2
  18.2%
Total Bilirubin, Grade 1
0
   0.0%
1
   9.1%
Total Bilirubin, Grade 2
1
   7.7%
0
   0.0%
Total Bilirubin, Grade 4
1
   7.7%
0
   0.0%
Triglycerides, Grade 2
0
   0.0%
2
  18.2%
Triglycerides, Grade 3
1
   7.7%
0
   0.0%
7.Secondary Outcome
Title Change From Baseline in Chemistry Parameters of ALT, ALP, AST and CK During the Randomized Treatment Phase
Hide Description Assessment was performed at Day 1, Week 12 and Week 24. Baseline was defined as the assessments done at Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Week 12 and 24) values.
Time Frame Baseline (Day 1), Week 12 and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title APL + OBT Placebo + OBT
Hide Arm/Group Description:
Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 13 11
Mean (Standard Deviation)
Unit of Measure: International unit per liter (IU/L)
ALT, Week 12 Number Analyzed 13 participants 4 participants
-7.231  (28.5048) 9.250  (18.8569)
ALT, Week 24 Number Analyzed 7 participants 0 participants
-5.429  (19.4324)
ALP, Week 12 Number Analyzed 13 participants 4 participants
-7.154  (24.1069) 25.750  (18.9275)
ALP, Week 24 Number Analyzed 7 participants 0 participants
-3.571  (19.4753)
AST, Week 12 Number Analyzed 13 participants 4 participants
-4.231  (15.9330) 4.750  (8.4212)
AST, Week 24 Number Analyzed 7 participants 0 participants
-3.857  (13.5699)
CK, Week 12 Number Analyzed 13 participants 4 participants
-3.462  (185.5095) 37.250  (78.9910)
CK, Week 24 Number Analyzed 7 participants 0 participants
102.714  (553.4250)
8.Secondary Outcome
Title Change From Baseline in Chemistry Parameters of CO2 Content/Bicarbonate, Chloride, Cholesterol, Glucose, High DL Cholesterol, LDL Cholesterol, Triglycerides, Potassium, Urea and Sodium During the Randomized Treatment Phase
Hide Description Assessment was performed at Day 1, Week 12 and Week 24. Baseline was defined as the assessments done at Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Week 12 and 24) values.
Time Frame Baseline (Day 1), Week 12 and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title APL + OBT Placebo + OBT
Hide Arm/Group Description:
Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 13 11
Mean (Standard Deviation)
Unit of Measure: Millimole (MMOL)/L
CO2 content/bicarbonate, Week 12 Number Analyzed 13 participants 4 participants
0.154  (2.5445) -1.250  (4.1932)
CO2 content/bicarbonate, Week 24 Number Analyzed 7 participants 0 participants
2.429  (3.6450)
Chloride, Week 12 Number Analyzed 13 participants 4 participants
0.462  (3.4306) -2.500  (2.6458)
Chloride, Week 24 Number Analyzed 7 participants 0 participants
0.857  (2.7946)
Cholesterol, Week 12 Number Analyzed 7 participants 1 participants
-0.200  (0.7095) -0.700 [1]   (NA)
Cholesterol, Week 24 Number Analyzed 7 participants 0 participants
-0.539  (0.8367)
Glucose, Week 12 Number Analyzed 13 participants 4 participants
0.415  (3.2246) 1.150  (1.3964)
Glucose, Week 24 Number Analyzed 7 participants 0 participants
-0.357  (1.8063)
HDL, Week 12 Number Analyzed 7 participants 1 participants
-0.036  (0.2340) -0.100 [1]   (NA)
HDL, Week 24 Number Analyzed 7 participants 0 participants
0.026  (0.2028)
LDL, Week 12 Number Analyzed 6 participants 1 participants
-0.552  (0.5635) -0.500 [1]   (NA)
LDL, Week 24 Number Analyzed 7 participants 0 participants
-0.597  (0.6607)
Potassium, Week 12 Number Analyzed 13 participants 4 participants
0.038  (0.3906) -0.225  (0.3304)
Potassium, Week 24 Number Analyzed 7 participants 0 participants
-0.114  (0.1952)
Sodium, Week 12 Number Analyzed 13 participants 4 participants
-0.846  (1.5730) -2.500  (3.6968)
Sodium, Week 24 Number Analyzed 7 participants 0 participants
0.714  (1.9760)
Triglycerides, Week 12 Number Analyzed 7 participants 1 participants
1.194  (1.3095) -0.240 [1]   (NA)
Triglycerides, Week 24 Number Analyzed 7 participants 0 participants
0.071  (0.7076)
Urea, Week 12 Number Analyzed 13 participants 11 participants
-0.162  (2.3835) 0.375  (2.9545)
Urea, Week 24 Number Analyzed 7 participants 0 participants
-0.343  (2.3572)
[1]
SD was not generated as only 1 participant was assessed during this time point.
9.Secondary Outcome
Title Change From Baseline in Chemistry Parameter of Creatinine and Total Bilirubin During the Randomized Treatment Phase
Hide Description Assessment was performed at Day 1, Week 12 and Week 24. Baseline was defined as the assessments done at Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Week 12 and 24) values.
Time Frame Baseline (Day 1), Week 12 and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title APL + OBT Placebo + OBT
Hide Arm/Group Description:
Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 13 11
Mean (Standard Deviation)
Unit of Measure: Micromole (UMOL)/L
Creatinine, Week 12 Number Analyzed 13 participants 4 participants
-1.385  (11.3397) 13.000  (11.1056)
Creatinine, Week 24 Number Analyzed 7 participants 0 participants
-2.714  (12.7504)
Total Bilirubin, Week 12 Number Analyzed 13 participants 4 participants
0.769  (18.8244) -0.500  (6.8069)
Total Bilirubin, Week 24 Number Analyzed 7 participants 0 participants
8.286  (31.0790)
10.Secondary Outcome
Title Change From Baseline in Chemistry Parameter of Albumin During the Randomized Treatment Phase
Hide Description Assessment was performed at Day 1, Week 12 and Week 24. Baseline was defined as the assessments done at Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Week 12 and 24) values.
Time Frame Baseline (Day 1), Week 12 and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed
Arm/Group Title APL + OBT Placebo + OBT
Hide Arm/Group Description:
Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 13 11
Mean (Standard Deviation)
Unit of Measure: Gram (g)/L
Week 12 Number Analyzed 13 participants 4 participants
1.385  (2.6627) 3.750  (2.5000)
Week 24 Number Analyzed 7 participants 0 participants
2.000  (3.5590)
11.Secondary Outcome
Title Change From Baseline in Chemistry Parameter of Lipase During the Randomized Treatment Phase
Hide Description Assessment was performed at Day 1, Week 12 and Week 24. Baseline was defined as the assessments done at Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Week 12 and 24) values.
Time Frame Baseline (Day 1), Week 12 and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title APL + OBT Placebo + OBT
Hide Arm/Group Description:
Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 13 11
Mean (Standard Deviation)
Unit of Measure: U/L
Week 12 Number Analyzed 11 participants 2 participants
6.636  (8.4531) 0.000  (4.2426)
Week 24 Number Analyzed 7 participants 0 participants
12.571  (20.3867)
12.Secondary Outcome
Title Change From Baseline in Haematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, White Blood Cell (WBC) Count During the Randomized Treatment Phase
Hide Description Assessment was performed at Day 1, Week 12 and Week 24. Baseline was defined as the assessments done at Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Week 12 and 24) values.
Time Frame Baseline (Day 1), Week 12 and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title APL + OBT Placebo + OBT
Hide Arm/Group Description:
Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 13 11
Mean (Standard Deviation)
Unit of Measure: Giga cells (GI)/L
Basophils, Week 12 Number Analyzed 13 participants 2 participants
-0.003  (0.0085) -0.005  (0.0212)
Basophils, Week 24 Number Analyzed 7 participants 0 participants
-0.000  (0.0153)
Eosinophils, Week 12 Number Analyzed 13 participants 2 participants
-0.027  (0.1013) 0.090  (0.1697)
Eosinophils, Week 24 Number Analyzed 7 participants 0 participants
-0.010  (0.0876)
Lymphocytes, Week 12 Number Analyzed 13 participants 2 participants
0.573  (0.4762) 0.050  (0.2970)
Lymphocytes, Week 24 Number Analyzed 7 participants 0 participants
0.373  (0.7915)
Monocytes, Week 12 Number Analyzed 13 participants 2 participants
0.041  (0.1398) -0.095  (0.2758)
Monocytes, Week 24 Number Analyzed 7 participants 0 participants
0.079  (0.0756)
Platelet Count, Week 12 Number Analyzed 13 participants 2 participants
47.846  (38.5202) -3.500  (33.2340)
Platelet Count, Week 24 Number Analyzed 7 participants 0 participants
70.143  (51.2199)
Total Neutrophils, Week 12 Number Analyzed 13 participants 2 participants
0.963  (1.0130) -0.935  (0.3889)
Total Neutrophils, Week 24 Number Analyzed 7 participants 0 participants
0.861  (0.9786)
WBC Count, Week 12 Number Analyzed 13 participants 2 participants
1.546  (1.1125) -0.900  (1.1314)
WBC Count, Week 24 Number Analyzed 7 participants 0 participants
1.300  (1.1015)
13.Secondary Outcome
Title Change From Baseline in Haematology Parameter of Mean Corpuscle Volume (MCV) During the Randomized Treatment Phase
Hide Description Assessment was performed at Day 1, Week 12 and Week 24. Baseline was defined as the assessments done at Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Week 12 and 24) values.
Time Frame Baseline (Day 1), Week 12 and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title APL + OBT Placebo + OBT
Hide Arm/Group Description:
Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 13 11
Mean (Standard Deviation)
Unit of Measure: Femtoliter (FL)
Week 12 Number Analyzed 13 participants 2 participants
-3.000  (7.7567) -1.500  (4.9497)
Week 24 Number Analyzed 7 participants 0 participants
-3.429  (9.5019)
14.Secondary Outcome
Title Change From Baseline in Haematology Parameter of Hematocrit During the Randomized Treatment Phase.
Hide Description Assessment was performed at Day 1, Week 12 and Week 24. Baseline was defined as the assessments done at Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Week 12 and 24) values.
Time Frame Baseline (Day 1), Week 12 and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title APL + OBT Placebo + OBT
Hide Arm/Group Description:
Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 13 11
Mean (Standard Deviation)
Unit of Measure: Percentage of red blood cells
Week 12 Number Analyzed 13 participants 2 participants
0.010  (0.0354) 0.026  (0.0099)
Week 24 Number Analyzed 7 participants 0 participants
-0.022  (0.0344)
15.Secondary Outcome
Title Change From Baseline in Haematology Parameter of Hemoglobin During the Randomized Treatment Phase
Hide Description Assessment was performed at Day 1, Week 12 and Week 24. Baseline was defined as the assessments done at Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Week 12 and 24) values.
Time Frame Baseline (Day 1), Week 12 and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title APL + OBT Placebo + OBT
Hide Arm/Group Description:
Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 13 11
Mean (Standard Deviation)
Unit of Measure: g/L
Week 12 Number Analyzed 13 participants 2 participants
4.923  (9.9621) 6.500  (4.9497)
Week 24 Number Analyzed 7 participants 0 participants
-4.000  (10.2144)
16.Secondary Outcome
Title Change From Baseline in Electrocardiograph (ECG) Parameter of Heart Rate (HR) During the Randomized Treatment Phase
Hide Description 12-lead ECG assessments were obtained at Day 1 (triplicate measurements), Week 4 and Week 24. The assessments were done using an ECG machine that automatically calculated the heart rate. Baseline was defined as the mean of the triplicate assessment done at Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Week 4 and 24) values.
Time Frame Baseline (Day 1), Week 4 and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title APL + OBT Placebo + OBT
Hide Arm/Group Description:
Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 13 11
Mean (Standard Deviation)
Unit of Measure: Beats per minute (Bpm)
Week 4 Number Analyzed 11 participants 10 participants
5.6  (12.74) 4.3  (11.54)
Week 24 Number Analyzed 6 participants 0 participants
-3.9  (8.11)
17.Secondary Outcome
Title Change From Baseline in ECG Parameter of RR Interval, Uncorrected QT Interval, QTc Interval (Fridericia), QTc Interval (Bazette), PR Interval and QRS Duration During the Randomized Treatment Phase
Hide Description 12-lead ECG assessments were obtained at Day 1 (triplicate measurements), Week 4 and Week 24. The assessments were done using an ECG machine that automatically measured RR, PR, QRS, uncorrected QT, QTc (Bazette) and QTc (Fridericia) intervals. Baseline was defined as the mean of the triplicate assessment done at Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Week 4 and Week 24) values.
Time Frame Baseline (Day 1), Week 4 and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title APL + OBT Placebo + OBT
Hide Arm/Group Description:
Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 13 11
Mean (Standard Deviation)
Unit of Measure: Millisecond (msec)
RR Interval, Week 4 Number Analyzed 11 participants 10 participants
-69.8  (112.21) -52.1  (128.19)
RR Interval, Week 24 Number Analyzed 6 participants 0 participants
52.2  (73.16)
Uncorrected QT Interval, Week 4 Number Analyzed 11 participants 10 participants
-18.3  (30.87) 1.2  (28.81)
Uncorrected QT Interval, Week 24 Number Analyzed 6 participants 0 participants
2.5  (12.49)
QTc Interval (Fridericia), Week 4 Number Analyzed 11 participants 10 participants
-9.3  (26.05) 10.2  (14.06)
QTc Interval (Fridericia), Week 24 Number Analyzed 6 participants 0 participants
-5.2  (13.00)
QTc Interval (Bazette), Week 4 Number Analyzed 11 participants 10 participants
-4.5  (27.68) 15.4  (14.64)
QTc Interval (Bazette), Week 24 Number Analyzed 6 participants 0 participants
-8.8  (17.47)
PR Interval, Week 4 Number Analyzed 11 participants 10 participants
-8.2  (16.24) 0.2  (15.98)
PR Interval, Week 24 Number Analyzed 6 participants 0 participants
2.5  (10.07)
QRS Duration, Week 4 Number Analyzed 11 participants 10 participants
3.2  (7.08) 0.4  (7.13)
QRS Duration, Week 24 Number Analyzed 6 participants 0 participants
-1.3  (7.68)
18.Secondary Outcome
Title Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Counts During the Randomized Treatment Phase
Hide Description The CD4 cell count is an indication of the strength of the immune system. The assessment of CD4 cell count was done by flow cytometry. Baseline was defined as the mean of the Baseline (Day 1) and pre-treatment visit values. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Week 12, 24 and 40) values.
Time Frame Baseline (Day 1), Week 12, Week 24 and Week 40
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title APL + OBT Placebo + OBT
Hide Arm/Group Description:
Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 13 11
Mean (Standard Deviation)
Unit of Measure: Cells/Cubic millimeter (mm^3)
Week 12 Number Analyzed 11 participants 2 participants
55.909  (53.8878) 80.500  (177.4838)
Week 24 Number Analyzed 7 participants 0 participants
27.000  (104.1441)
Week 40 Number Analyzed 3 participants 0 participants
153.000  (57.6888)
19.Secondary Outcome
Title Time to Centres for Disease Control and Prevention (CDC) Class C Acquired Immune Deficiency Syndrome (AIDS)-Defining Event or Death
Hide Description The time to CDC class C AIDS-defining event or death was planned to be assessed as per the CDC 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. The CDC classifies HIV infection as Category A (participants with asymptomatic HIV infection, acute HIV infection with accompanying illness, or persistent generalized lymphadenopathy), Category B (participants with symptomatic non-AIDS condition, i.e., conditions that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or conditions are considered by physicians to have a clinical course or to require management that is complicated by HIV infection), and Category C (includes AIDS indicator conditions as defined by diagnostic or presumptive measures).
Time Frame Up to Week 12 Follow-up of the Randomized phase, up to Week 12 Follow-up of the Open Labeled Non-Randomized phase and every 6 months Follow-up of off study drug/on study phase
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Data were not collected for this outcome measure due to early termination of the study.
Arm/Group Title APL + OBT Placebo + OBT
Hide Arm/Group Description:
Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
20.Secondary Outcome
Title Number of Participants With Development of Antiretroviral Resistance to GW873140 400 mg BID and Other Antiretroviral Drugs
Hide Description Assessment for the development of antiretroviral resistance was performed at each visit up to Follow-up. The genotypic analysis of viral resistance associated mutations was done using protease and reverse transcriptase enzymes. The number of participants with treatment emergent changes in reverse transcriptase and protease genotypic mutations were reported.
Time Frame Up to Follow-up (Week 52)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Virologic Failure Population was defined as the number of participants with protocol defined virologic failure criteria.
Arm/Group Title APL + OBT Placebo + OBT
Hide Arm/Group Description:
Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 6 3
Measure Type: Count of Participants
Unit of Measure: Participants
2
  33.3%
1
  33.3%
21.Secondary Outcome
Title Number of Participants With 50% Inhibitory Concentration (IC50) Fold Resistance at Baseline
Hide Description The IC50 is a measure of the effectiveness of a substance in inhibiting a specific biological or biochemical function. IC50 was collected for abacavir (ABC), atazanavir (ATV), delavirdine (DLV), didanosine (DDI), efavirenz (EFV), emtricitabine, enfuvirtide , fosamprenavir (AMP), GW873140 (APL), indinavir (IDV), indinavir rooted with ritonavir (IDV/r), lamivudine, lopinavir rooted with ritonavir (LPV/r), nelfinavir (NFV), nevirapine (NVP), ritonavir (RTV), saquinavir (SQV), stavudine, tenofovir (TFV), tipranavir rooted with ritonavir (TPV/r), zidovudine (ZDV). Data is categorized for number of participants with each IC50 concentration of the individual drugs at Baseline (Day 1).
Time Frame Baseline (Day 1)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title APL + OBT Placebo + OBT
Hide Arm/Group Description:
Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 13 11
Measure Type: Count of Participants
Unit of Measure: Participants
ABC < 4.5
0
   0.0%
4
  36.4%
ABC >= 4.5
13
 100.0%
7
  63.6%
ATV < 2.3
1
   7.7%
3
  27.3%
ATV >= 2.3
12
  92.3%
8
  72.7%
ATV/r < 5.2
1
   7.7%
5
  45.5%
ATV/r >= 5.2
12
  92.3%
6
  54.5%
DLV < 2.5
3
  23.1%
4
  36.4%
DLV >= 2.5
10
  76.9%
7
  63.6%
DDI < 1.3
0
   0.0%
5
  45.5%
DDI >= 1.3
13
 100.0%
6
  54.5%
EFV < 2.5
2
  15.4%
2
  18.2%
EFV >= 2.5
11
  84.6%
9
  81.8%
Emtricitabine < 3.5
0
   0.0%
3
  27.3%
Emtricitabine >= 3.5
13
 100.0%
8
  72.7%
Enfuvirtide < 2.5
2
  15.4%
7
  63.6%
Enfuvirtide >= 2.5
9
  69.2%
2
  18.2%
AMP < 2
1
   7.7%
4
  36.4%
AMP >= 2
12
  92.3%
7
  63.6%
APL < 2.5
12
  92.3%
9
  81.8%
APL >= 2.5
0
   0.0%
0
   0.0%
IDV < 2.1
1
   7.7%
3
  27.3%
IDV >= 2.1
12
  92.3%
8
  72.7%
IDV/r < 10
2
  15.4%
7
  63.6%
IDV/r >= 10
11
  84.6%
4
  36.4%
Lamivudine < 3.5
0
   0.0%
4
  36.4%
Lamivudine >= 3.5
13
 100.0%
7
  63.6%
LPV/r < 10
3
  23.1%
6
  54.5%
LPV/r >= 10
10
  76.9%
5
  45.5%
NFV < 2.5
1
   7.7%
3
  27.3%
NFV >= 2.5
12
  92.3%
8
  72.7%
NVP < 2.5
1
   7.7%
2
  18.2%
NVP >= 2.5
12
  92.3%
9
  81.8%
RTV < 2.5
1
   7.7%
3
  27.3%
RTV >= 2.5
12
  92.3%
8
  72.7%
SQV < 1.7
1
   7.7%
3
  27.3%
SQV >= 1.7
12
  92.3%
8
  72.7%
Stavudine < 1.7
1
   7.7%
5
  45.5%
Stavudine >= 1.7
12
  92.3%
6
  54.5%
TFV < 1.4
4
  30.8%
4
  36.4%
TFV >= 1.4
9
  69.2%
7
  63.6%
TPV/r < 4
7
  53.8%
7
  63.6%
TPV/r >= 4
6
  46.2%
3
  27.3%
ZDV < 1.9
1
   7.7%
3
  27.3%
ZDV >= 1.9
12
  92.3%
8
  72.7%
22.Secondary Outcome
Title Plasma GW873140 400 mg BID Pharmacokinetic (PK) Parameter of Area Under the Plasma Concentration-time Curve During One Dosing Interval of Length (Tau) (AUC [0-tau]) During the Randomized Treatment Phase
Hide Description AUC (0- tau) GW873140 was defined as the area under the plasma concentration-time curve from time 0 to tau. Blood samples for evaluation of GW873140 plasma PK was planned to be collected from all participants at Week 4, 12, and 24. Intensive PK sampling was planned to be conducted with the enrolled participants. All participants who were not part of the intensive PK group was planned to be part of the limited PK sample group. Participants were supposed to complete a diary card with the date and time of investigational product administration of the last dose prior to clinic visits on Weeks 4, 12, and 24. It was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.
Time Frame Week 4 (pre-dose [0 hour], 1, 2, 3, 4, 6, 8, 10 hour post-evening dose), Week 12 (pre-dose [0 hour] and 2-4 hour post-morning dose) and Week 24 (pre-dose and 2-4 hour post-morning dose)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The PK Population was defined as all participants who received GW873140 and underwent plasma PK sampling during the study. Participants for whom plasma a PK sample was obtained and assayed were planned to be included in analyses of the PK population. Data were not collected for this outcome measure due to early termination of the study.
Arm/Group Title APL + OBT
Hide Arm/Group Description:
Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
23.Secondary Outcome
Title Plasma GW873140 400 mg BID PK Parameter of Maximum Observed Plasma Concentration (Cmax) During the Randomized Treatment Phase
Hide Description Cmax is defined as the first occurrence of the maximum observed plasma concentration determined directly from the raw concentration-time data. Blood samples for evaluation of GW873140 plasma PK was planned to be collected from all participants at Week 4, 12, and 24. Intensive PK sampling was planned to be conducted with the enrolled participants. All participants who were not part of the intensive PK group was planned to be part of the limited PK sample group. Participants were supposed to complete a diary card with the date and time of investigational product administration of the last dose prior to clinic visits on Weeks 4, 12, and 24.
Time Frame Week 4 (pre-dose [0 hour], 1, 2, 3, 4, 6, 8, 10 hour post-evening dose), Week 12 (pre-dose [0 hour] and 2-4 hour post-morning dose) and Week 24 (pre-dose and 2-4 hour post-morning dose)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Population. Data were not collected for this outcome measure due to early termination of the study.
Arm/Group Title APL + OBT
Hide Arm/Group Description:
Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
24.Secondary Outcome
Title Plasma GW873140 400 mg BID PK Parameter of Time of Maximum Observed Plasma Concentration (Tmax) During the Randomized Treatment Phase
Hide Description Tmax is defined as the time at which Cmax is observed, determined directly from the raw concentration-time data. Blood samples for evaluation of GW873140 plasma PK was planned to be collected from all participants at Week 4, 12, and 24. Intensive PK sampling was planned to be conducted with the enrolled participants. All participants who were not part of the intensive PK group was planned to be part of the limited PK sample group. Participants were supposed to complete a diary card with the date and time of investigational product administration of the last dose prior to clinic visits on Weeks 4, 12, and 24.
Time Frame Week 4 (pre-dose [0 hour], 1, 2, 3, 4, 6, 8, 10 hour post-evening dose), Week 12 (pre-dose [0 hour] and 2-4 hour post-morning dose) and Week 24 (pre-dose and 2-4 hour post-morning dose)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Population. Data were not collected for this outcome measure due to early termination of the study.
Arm/Group Title APL + OBT
Hide Arm/Group Description:
Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
25.Secondary Outcome
Title Plasma GW873140 400 mg BID PK Parameter of Concentration at End of Dosing Interval (Trough Concentration [Cτ]) During the Randomized Treatment Phase
Hide Description Blood samples for evaluation of GW873140 plasma PK was planned to be collected from all participants at Week 4, 12, and 24. Intensive PK sampling was planned to be conducted with the enrolled participants. All participants who were not part of the intensive PK group was planned to be part of the limited PK sample group. Participants were supposed to complete a diary card with the date and time of investigational product administration of the last dose prior to clinic visits on Weeks 4, 12, and 24.
Time Frame Week 4 (pre-dose [0 hour], 1, 2, 3, 4, 6, 8, 10 hour post-evening dose), Week 12 (pre-dose [0 hour] and 2-4 hour post-morning dose) and Week 24 (pre-dose and 2-4 hour post-morning dose)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Population. Data were not collected for this outcome measure due to early termination of the study.
Arm/Group Title APL + OBT
Hide Arm/Group Description:
Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
26.Secondary Outcome
Title Investigational Product Adherence Measured by Pill Counts
Hide Description Adherence to investigational product was planned to be evaluated using pill counts of unused investigational product (blinded GW873140 or placebo, open-label GW873140 for open label phase). This assessment was planned to be conducted at each time the participant received a new (refill) supply of study medication.
Time Frame Up to Week 48 of Randomized Treatment phase and up to Switch + 24 Weeks of the Open Labeled phase
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Data for this outcome measure were not collected due to early termination of the study.
Arm/Group Title APL + OBT Placebo + OBT
Hide Arm/Group Description:
Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
27.Secondary Outcome
Title Number of Participants Who Were Bothered by Each of Several Specific Symptoms Evaluated Using the HIV Symptom Index Questionnaire During the Randomized Treatment Phase
Hide Description The HIV Symptom Index Questionnaire was planned to be used to evaluate how bothersome certain symptoms were during the conduct of this clinical study. The participant self-report instrument had 20 items, each of which asked about a specific symptom or group of related symptoms that participants might have had during the past 4 weeks and the degree to which the participant is bothered by the symptom. The symptom index comprised 32 common and HIV-specific symptoms scored in terms of presence/absence (1, 0) and severity on a 4-point scale (0 = not at all to 3 =quite a bit). Higher score represented greater severity of symptoms.
Time Frame Upto Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Data for this outcome measure were not collected due to early termination of the study.
Arm/Group Title APL + OBT Placebo + OBT
Hide Arm/Group Description:
Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
28.Secondary Outcome
Title Number of Participants With the Impact on Health Related Quality of Life Measured by Euro Quality of Life (Qol) Questionnaire During the Randomized Treatment Phase
Hide Description The EuroQol is a standardized instrument for use as a measure of health related quality of life. It consists of two pages comprising the EuroQoL 5 Dimension 5 level (EQ-5D5) descriptive system and the EQ visual analogue scale (VAS). The EQ-5D5 comprises of five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and depression/anxiety). Each dimension comprises five levels of response (no problems, mild problems, moderate problems, moderate to extreme problems, and extreme problems). The EQ VAS records the respondents self-rated health status on a vertical graduated (0 to 100) VAS. Higher score represented greater severity of diseases.
Time Frame Up to Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Data for this outcome measure were not collected due to early termination of the study.
Arm/Group Title APL + OBT Placebo + OBT
Hide Arm/Group Description:
Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame AE's were collected up to Follow-up (Week 52)
Adverse Event Reporting Description ITT Population was used.
 
Arm/Group Title APL + OBT Placebo + OBT
Hide Arm/Group Description Participants were administered APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug. Participants were administered matching placebo to APL tablets orally as 400 mg BID for 48 Weeks. Each dose was to be given with food. The OBT regimen was chosen by the investigator prior to randomization, based on the participant’s prior treatment history, screening genotypic and phenotypic resistance testing results, and any prior resistance testing results if available. The drugs in the OBT regimen was chosen from the locally available ART and consisted between three and six drugs, one of which was RTV-boosted PI. Low-dose RTV did not count as one of the OBT regimen drugs and RTV doses of >400 mg/day were not permitted. FDC was counted according to the number of compounds making up the FDC (e.g., combivir counted as two drugs [lamivudine and zidovudine], trizivir counted as three drugs, etc.). Kaletra (LPV/RTV) was counted as one drug.
All-Cause Mortality
APL + OBT Placebo + OBT
Affected / at Risk (%) Affected / at Risk (%)
Total   0/13 (0.00%)   0/11 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
APL + OBT Placebo + OBT
Affected / at Risk (%) Affected / at Risk (%)
Total   0/13 (0.00%)   0/11 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
APL + OBT Placebo + OBT
Affected / at Risk (%) Affected / at Risk (%)
Total   11/13 (84.62%)   5/11 (45.45%) 
Blood and lymphatic system disorders     
Lymphadenopathy  1  1/13 (7.69%)  0/11 (0.00%) 
Gastrointestinal disorders     
Diarrhoea  1  7/13 (53.85%)  2/11 (18.18%) 
Nausea  1  3/13 (23.08%)  1/11 (9.09%) 
Abdominal pain  1  1/13 (7.69%)  1/11 (9.09%) 
Abdominal tenderness  1  1/13 (7.69%)  0/11 (0.00%) 
Aphthous stomatitis  1  1/13 (7.69%)  0/11 (0.00%) 
Constipation  1  0/13 (0.00%)  1/11 (9.09%) 
Flatulence  1  1/13 (7.69%)  0/11 (0.00%) 
Gastrooesophageal reflux disease  1  1/13 (7.69%)  0/11 (0.00%) 
Rectal lesion  1  1/13 (7.69%)  0/11 (0.00%) 
Stomach discomfort  1  1/13 (7.69%)  0/11 (0.00%) 
General disorders     
Fatigue  1  2/13 (15.38%)  0/11 (0.00%) 
Pyrexia  1  1/13 (7.69%)  1/11 (9.09%) 
Chills  1  1/13 (7.69%)  0/11 (0.00%) 
Hernia  1  1/13 (7.69%)  0/11 (0.00%) 
Influenza like illness  1  1/13 (7.69%)  0/11 (0.00%) 
Injection site pain  1  0/13 (0.00%)  1/11 (9.09%) 
Injection site reaction  1  0/13 (0.00%)  1/11 (9.09%) 
Pain  1  1/13 (7.69%)  0/11 (0.00%) 
Infections and infestations     
Sinusitis  1  1/13 (7.69%)  1/11 (9.09%) 
Acarodermatitis  1  1/13 (7.69%)  0/11 (0.00%) 
Bronchitis  1  1/13 (7.69%)  0/11 (0.00%) 
Eye infection  1  1/13 (7.69%)  0/11 (0.00%) 
Herpes simplex  1  0/13 (0.00%)  1/11 (9.09%) 
Oropharyngeal candidiasis  1  0/13 (0.00%)  1/11 (9.09%) 
Otitis media  1  1/13 (7.69%)  0/11 (0.00%) 
Tinea cruris  1  0/13 (0.00%)  1/11 (9.09%) 
Upper respiratory tract infection  1  1/13 (7.69%)  0/11 (0.00%) 
Metabolism and nutrition disorders     
Diabetes mellitus  1  1/13 (7.69%)  0/11 (0.00%) 
Increased appetite  1  0/13 (0.00%)  1/11 (9.09%) 
Musculoskeletal and connective tissue disorders     
Joint crepitation  1  1/13 (7.69%)  0/11 (0.00%) 
Muscle spasms  1  1/13 (7.69%)  0/11 (0.00%) 
Neck pain  1  1/13 (7.69%)  0/11 (0.00%) 
Nervous system disorders     
Headache  1  3/13 (23.08%)  0/11 (0.00%) 
Dysgeusia  1  1/13 (7.69%)  0/11 (0.00%) 
Migraine  1  1/13 (7.69%)  0/11 (0.00%) 
Neuropathy peripheral  1  1/13 (7.69%)  0/11 (0.00%) 
Paraesthesia  1  1/13 (7.69%)  0/11 (0.00%) 
Psychiatric disorders     
Anxiety  1  1/13 (7.69%)  0/11 (0.00%) 
Depression  1  1/13 (7.69%)  0/11 (0.00%) 
Insomnia  1  1/13 (7.69%)  0/11 (0.00%) 
Restlessness  1  1/13 (7.69%)  0/11 (0.00%) 
Reproductive system and breast disorders     
Erectile dysfunction  1  1/13 (7.69%)  0/11 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Epistaxis  1  1/13 (7.69%)  0/11 (0.00%) 
Nasal ulcer  1  1/13 (7.69%)  0/11 (0.00%) 
Sinus congestion  1  1/13 (7.69%)  0/11 (0.00%) 
Skin and subcutaneous tissue disorders     
Dermatitis allergic  1  0/13 (0.00%)  1/11 (9.09%) 
Lipodystrophy acquired  1  0/13 (0.00%)  1/11 (9.09%) 
Rash generalised  1  1/13 (7.69%)  0/11 (0.00%) 
1
Term from vocabulary, MedDRA 10.0
Indicates events were collected by systematic assessment
Study was early terminated prior to the completion of enrollment due to treatment-emergent hepatotoxicity that occurred among some participants receiving APL.
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
Name/Title: GSK Response Center
Organization: ViiV Healthcare
Phone: 866-435-7343
Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT00197145     History of Changes
Other Study ID Numbers: CCR102709
First Submitted: September 13, 2005
First Posted: September 20, 2005
Results First Submitted: August 18, 2017
Results First Posted: November 2, 2018
Last Update Posted: November 2, 2018