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Trial of Maraviroc (UK-427,857) in Combination With Optimized Background Therapy Versus Optimized Background Therapy Alone for the Treatment of Antiretroviral-Experienced NonCCR5-Tropic HIV-1 Infected Subjects

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ClinicalTrials.gov Identifier: NCT00098748
Recruitment Status : Completed
First Posted : December 8, 2004
Results First Posted : October 21, 2010
Last Update Posted : December 7, 2010
Sponsor:
Collaborator:
Pfizer
Information provided by:
ViiV Healthcare

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition HIV Infections
Interventions Drug: Optimized Background Therapy (OBT)
Drug: maraviroc (UK-427,857)
Enrollment 190
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening. Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening. Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.
Period Title: Assigned to Study Treatment
Started 63 63 64
Completed 63 61 62
Not Completed 0 2 2
Reason Not Completed
Randomized, but not treated             0             2             2
Period Title: Received Study Treatment
Started 63 61 [1] 62 [2]
Dual-tropic Subjects by Phenotype Assay 57 [3] 52 58
Completed 15 25 18
Not Completed 48 36 44
Reason Not Completed
Death             2             1             2
Adverse Event             1             2             5
Lack of Efficacy             40             27             27
Other             2             2             6
Subject defaulted             3             4             4
[1]
Due to 1 placebo subject switched to maraviroc BID, BID = 62 subjects in Adverse event tables.
[2]
Due to 1 placebo subject switched to maraviroc BID, Placebo = 61 subjects in Adverse event tables.
[3]
Dual-tropic: Virus capable of using both CCR5 and CXCR4 coreceptors for cell entry.
Period Title: Continued on Open-Label Treatment
Started 15 25 0 [1]
Completed 7 10 0
Not Completed 8 15 0
Reason Not Completed
Adverse Event             0             1             0
Lack of Efficacy             1             2             0
Other reason includes protocol violation             6             7             0
Lost to Follow-up             1             1             0
Withdrawal by Subject             0             4             0
[1]
Placebo group not offered open-label maraviroc due to study not reaching primary endpoint at Week 24
Arm/Group Title Maraviroc QD Maraviroc BID Placebo Total
Hide Arm/Group Description Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening. Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening. Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening. Total of all reporting groups
Overall Number of Baseline Participants 63 61 62 186
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 63 participants 61 participants 62 participants 186 participants
<18 years 2 2 0 4
Between 18 and 24 years 1 1 1 3
Between 25 and 34 years 2 3 2 7
Between 35 and 44 years 30 31 31 92
Between 45 and 54 years 25 21 20 66
Between 55 and 64 years 3 3 7 13
≥65 years 0 0 1 1
Age Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 63 participants 61 participants 62 participants 186 participants
42.7
(16 to 59)
42.5
(16 to 62)
44.6
(23 to 65)
43.3
(16 to 65)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 63 participants 61 participants 62 participants 186 participants
Female
10
  15.9%
6
   9.8%
9
  14.5%
25
  13.4%
Male
53
  84.1%
55
  90.2%
53
  85.5%
161
  86.6%
1.Primary Outcome
Title Change From Baseline in Human Immunodeficiency Virus (HIV-1) Viral Load (Ribonucleic Acid [RNA])
Hide Description Change from baseline in log 10-transformed plasma viral load (HIV-1 RNA) levels (log 10 copies per milliliter [log10 copies/mL]). Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and baseline visits.
Time Frame Baseline to Week 24 and Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS)-as treated: all randomized subjects classified as dual-tropic by phenotype assay; received at least 1 dose of study treatment. Missing values: discontinuations (DC) imputed as baseline value (change from baseline=0); missing data imputed as Last Observation Carried Forward (LOCF).
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.
Overall Number of Participants Analyzed 57 52 58
Mean (Standard Error)
Unit of Measure: log10 copies/mL
Week 24 -0.890  (0.1706) -1.194  (0.2060) -0.953  (0.1795)
Week 48 -0.604  (0.1596) -1.105  (0.2071) 0.839  (0.1851)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments Maraviroc (MVC) QD versus placebo (PBO) treatment (TX) difference at Week 24. If upper bound of 97.5% confidence interval is <0, it is concluded that dose is superior to PBO. If upper bound is <0.25, it is concluded that MVC is non-inferior to PBO. Assumption: 79% of subjects are dual-tropic; total N=192 needed to be randomized to get N=150 dual-tropic. Standard deviation=0.8 with 2-sided p-value=0.025: 80% power for TX difference of 0.5 for change from baseline in log10-transformed viral load.
Type of Statistical Test Non-Inferiority or Equivalence
Comments For hypothesis of superiority, if upper bound of 97.5% confidence interval (CI) of TX difference was <0 log10 copies/mL, it was concluded that MVC regimen was superior to PBO meaning that MVC added to Optimized Background Therapy (OBT) provides an additional reduction in plasma HIV-1 RNA compared to OBT alone. If superiority could not be concluded, then a hypothesis of noninferiority was tested. If upper bound of CI is <0.25 log10 copies/mL, noninferiority of MVC regimen to placebo was claimed.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments TX difference adjusted for randomization strata. Bonferroni adjustment for multiple comparisons by use of 2-sided 97.5% CI to maintain alpha=0.05.
Method of Estimation Estimation Parameter Least squares mean
Estimated Value 0.055
Confidence Interval (2-Sided) 97.5%
-0.528 to 0.638
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.2575
Estimation Comments Negative values for change from baseline=benefit of TX; negative values for MVC versus (vs) PBO=advantage of MVC.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments MVC BID vs PBO treatment difference at Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments TX difference adjusted for randomization strata. Bonferroni adjustment for multiple comparisons by use of 2-sided 97.5% CI to maintain alpha=0.05.
Method of Estimation Estimation Parameter Least squares mean
Estimated Value -0.232
Confidence Interval (2-Sided) 97.5%
-0.829 to 0.364
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.2637
Estimation Comments Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments MVC QD vs PBO treatment difference at Week 48.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments TX difference adjusted for randomization strata. Bonferroni adjustment for multiple comparisons by use of 2-sided 97.5% CI to maintain alpha=0.05.
Method of Estimation Estimation Parameter Least squares mean
Estimated Value 0.229
Confidence Interval (2-Sided) 97.5%
-0.351 to 0.810
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.2567
Estimation Comments Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments MVC BID vs PBO treatment difference at Week 48.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments TX difference adjusted for randomization strata. Bonferroni adjustment for multiple comparisons by use of 2-sided 97.5% CI to maintain alpha=0.05.
Method of Estimation Estimation Parameter Least squares mean
Estimated Value -0.261
Confidence Interval (2-Sided) 97.5%
-0.856 to 0.333
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.2628
Estimation Comments Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.
2.Secondary Outcome
Title Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL
Hide Description [Not Specified]
Time Frame Week 24, Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS - as treated dual-tropic subjects. Missing values counted as failures/non-responders (counted as not achieving the stated criterion).
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.
Overall Number of Participants Analyzed 57 52 58
Measure Type: Number
Unit of Measure: participants
Week 24 14 16 14
Week 48 13 16 13
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments MVC QD vs PBO treatment difference in proportions at Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in proportions
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
-0.12 to 0.18
Estimation Comments The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments MVC BID vs PBO treatment difference in proportions at Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in proportions
Estimated Value 0.07
Confidence Interval (2-Sided) 95%
-0.08 to 0.23
Estimation Comments The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments MVC QD vs PBO treatment difference in proportions at Week 48.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in proportions
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
-0.12 to 0.17
Estimation Comments The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments MVC BID vs PBO treatment difference in proportions at Week 48.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in proportions
Estimated Value 0.09
Confidence Interval (2-Sided) 95%
-0.07 to 0.25
Estimation Comments The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.
3.Secondary Outcome
Title Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 0.5 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels
Hide Description Number of subjects with HIV-1 RNA levels < 400 copies/mL or at least 0.5 log 10-transformed decrease from baseline in HIV-1 RNA levels. Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and baseline visits.
Time Frame Baseline, Week 24, Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS-as treated dual-tropic subjects. Missing values counted as failures/non-responders (counted as not achieving the stated criterion).
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.
Overall Number of Participants Analyzed 57 52 58
Measure Type: Number
Unit of Measure: participants
Week 24 24 25 23
Week 48 14 22 18
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments MVC QD vs PBO treatment difference in proportions at Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in proportions
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
-0.15 to 0.20
Estimation Comments The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments MVC BID vs PBO treatment difference in proportions at Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in proportions
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
-0.10 to 0.26
Estimation Comments The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments MVC QD vs PBO treatment difference in proportions at Week 48.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in proportions
Estimated Value -0.06
Confidence Interval (2-Sided) 95%
-0.22 to 0.10
Estimation Comments The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments MVC BID vs PBO treatment difference in proportions at Week 48.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in proportions
Estimated Value 0.11
Confidence Interval (2-Sided) 95%
-0.07 to 0.28
Estimation Comments The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.
4.Secondary Outcome
Title Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 1.0 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels
Hide Description Number of subjects with HIV-1 RNA levels < 400 copies/mL or at least 1.0 log 10-transformed decrease from baseline in HIV-1 RNA levels. Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and baseline visits.
Time Frame Baseline, Week 24, Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS-as treated dual-tropic subjects. Missing values counted as failures/non-responders (counted as not achieving the stated criterion).
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.
Overall Number of Participants Analyzed 57 52 58
Measure Type: Number
Unit of Measure: participants
Week 24 18 23 21
Week 48 13 20 15
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments MVC QD vs PBO treatment difference in proportions at Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in proportions
Estimated Value -0.05
Confidence Interval (2-Sided) 95%
-0.21 to 0.12
Estimation Comments The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments MVC BID vs PBO treatment difference in proportions at Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in proportions
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
-0.10 to 0.26
Estimation Comments The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments MVC QD vs PBO treatment difference in proportions at Week 48.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in proportions
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.18 to 0.13
Estimation Comments The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments MVC BID vs PBO treatment difference in proportions at Week 48.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in proportions
Estimated Value 0.12
Confidence Interval (2-Sided) 95%
-0.04 to 0.29
Estimation Comments The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.
5.Secondary Outcome
Title Number of Subjects With HIV-1 RNA Levels < 50 Copies/mL
Hide Description [Not Specified]
Time Frame Baseline, Week 24, Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS - as treated dual-tropic subjects. Missing values counted as failures/non-responders (counted as not achieving the stated criterion).
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.
Overall Number of Participants Analyzed 57 52 58
Measure Type: Number
Unit of Measure: participants
Week 24 12 14 9
Week 48 10 14 13
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments MVC QD vs PBO treatment difference in proportions at Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in proportions
Estimated Value 0.07
Confidence Interval (2-Sided) 95%
-0.07 to 0.20
Estimation Comments The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments MVC BID vs PBO difference in proportions at Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in proportions
Estimated Value 0.11
Confidence Interval (2-Sided) 95%
-0.03 to 0.26
Estimation Comments The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments MVC QD vs PBO treatment difference in proportions at Week 48.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in proportions
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.18 to 0.10
Estimation Comments The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments MVC BID vs PBO treatment difference in proportions at Week 48.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in proportions
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.10 to 0.21
Estimation Comments The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.
6.Secondary Outcome
Title Change From Baseline in CD4 Cell Count
Hide Description Change from baseline in CD4 cell count (measured as cells per microliter [cells/µL]). Baseline value calculated as the average of pre-dose measurements collected at screening, randomization, and baseline visits.
Time Frame Baseline to Week 24 and Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS - as treated dual-tropic subjects. Placebo N: 4 subjects did not have on-treatment information. Missing data imputed using LOCF.
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.
Overall Number of Participants Analyzed 57 52 54
Mean (Standard Error)
Unit of Measure: cells/µL
Week 24 59.237  (8.9661) 62.651  (10.0234) 36.367  (8.4477)
Week 48 65.86  (10.822) 78.87  (11.566) 51.29  (12.523)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments MVC QD vs PBO treatment difference at Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments TX difference adjusted for randomization strata.
Method of Estimation Estimation Parameter Least squares mean
Estimated Value 23.927
Confidence Interval (2-Sided) 95%
-1.359 to 49.213
Parameter Dispersion
Type: Standard Error of the mean
Value: 12.8025
Estimation Comments Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments MVC BID vs PBO treatment difference at Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments TX difference adjusted for randomization strata.
Method of Estimation Estimation Parameter Least squares mean
Estimated Value 26.679
Confidence Interval (2-Sided) 95%
0.869 to 52.490
Parameter Dispersion
Type: Standard Error of the mean
Value: 13.0678
Estimation Comments Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments MVC QD vs PBO treatment difference at Week 48.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments TX difference adjusted for randomization strata.
Method of Estimation Estimation Parameter Least squares mean
Estimated Value 14.61
Confidence Interval (2-Sided) 95%
-17.80 to 47.03
Parameter Dispersion
Type: Standard Error of the mean
Value: 16.412
Estimation Comments Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments MVC BID vs PBO treatment difference at Week 48.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments TX difference adjusted for randomization strata.
Method of Estimation Estimation Parameter Least squares mean
Estimated Value 27.71
Confidence Interval (2-Sided) 95%
-5.38 to 60.80
Parameter Dispersion
Type: Standard Error of the mean
Value: 16.754
Estimation Comments Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.
7.Secondary Outcome
Title Change From Baseline in CD8 Cell Count
Hide Description Change from baseline in CD8 cell count (measured as cells/µL). Baseline value calculated as the average of pre-dose measurements collected at screening, randomization, and baseline visits.
Time Frame Baseline to Week 24 and Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS - as treated dual-tropic subjects. Placebo N: 4 subjects did not have on-treatment information. Missing data imputed using LOCF.
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.
Overall Number of Participants Analyzed 57 52 54
Mean (Standard Error)
Unit of Measure: cells/µL
Week 24 391.061  (57.0135) 322.683  (68.3315) 154.293  (46.8100)
Week 48 351.23  (54.653) 342.87  (72.222) 192.30  (62.578)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments MVC QD vs PBO treatment difference at Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments TX difference adjusted for randomization strata.
Method of Estimation Estimation Parameter Least squares mean
Estimated Value 234.499
Confidence Interval (2-Sided) 95%
74.913 to 394.084
Parameter Dispersion
Type: Standard Error of the mean
Value: 80.7990
Estimation Comments Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments MVC BID vs PBO treatment difference at Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments TX difference adjusted for randomization strata.
Method of Estimation Estimation Parameter Least squares mean
Estimated Value 188.817
Confidence Interval (2-Sided) 95%
23.999 to 353.635
Parameter Dispersion
Type: Standard Error of the mean
Value: 83.4484
Estimation Comments Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments MVC QD vs PBO treatment difference at Week 48.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments TX difference adjusted for randomization strata.
Method of Estimation Estimation Parameter Least squares mean
Estimated Value 155.94
Confidence Interval (2-Sided) 95%
-16.49 to 328.37
Parameter Dispersion
Type: Standard Error of the mean
Value: 87.304
Estimation Comments Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments MVC BID vs PBO treatment difference at Week 48.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments TX difference adjusted for randomization strata.
Method of Estimation Estimation Parameter Least squares mean
Estimated Value 182.91
Confidence Interval (2-Sided) 95%
4.81 to 361.02
Parameter Dispersion
Type: Standard Error of the mean
Value: 90.174
Estimation Comments Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.
8.Secondary Outcome
Title Time (50% Quartile Point Estimate) to Virologic Failure
Hide Description Time to virologic failure based on observed HIV-1 RNA levels and failure events (death; permanent discontinuation of test drug [perm DC]; lost to follow-up [LTFU]; new anti-retroviral drug added (except background drug change to drug of same class); or on open label for early non-response or rebound). Failure: at Time 0 if level not <400 copies/mL (2 consecutive visits) before event(s) or last available visit; at time of earliest event if level <400 copies/mL (on 2 consecutive visits); failure if level ≥400 copies/mL (2 consecutive visits) or 1 visit ≥400 copies/mL followed by perm DC or LTFU.
Time Frame Day 1 through Week 24 and through Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS - as treated dual-tropic subjects; (n)=number of subjects with virologic failure at observation for maraviroc QD, maraviroc BID, and placebo, respectively; Week 48 result values (0.00)=virologic failure at Day 0.
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.
Overall Number of Participants Analyzed 57 52 58
Median (95% Confidence Interval)
Unit of Measure: days
Week 24 (n=35, 23, 29)
88.00 [1] 
(59.00 to NA)
189.00
(113.00 to 189.00)
100.00 [1] 
(60.00 to NA)
Week 48 (n=45, 37, 44)
0.00 [2] 
(NA to NA)
0.00
(0.00 to 142.00)
0.00
(0.00 to 29.00)
[1]
Parameter was not calculable.
[2]
Parameters were not calculable.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments MVC QD vs PBO at Week 24. Kaplan-Meier survival estimates. TX difference evaluated by log-rank test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7524
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments MVC BID vs PBO at Week 24. Kaplan-Meier survival estimates. TX difference evaluated by log-rank test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2540
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments MVC QD vs PBO at Week 48. Kaplan-Meier survival estimates. TX difference evaluated by log-rank test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8243
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments MVC BID vs PBO at Week 48. Kaplan-Meier survival estimates. TX difference evaluated by log-rank test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6657
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in Time Averaged Difference (TAD) in log10 HIV-1 RNA
Hide Description Change from baseline of TAD in log10 HIV-1 RNA viral load calculated as [AUC of HIV-1 RNA viral load (log10 copies/mL) / time period] - Baseline HIV-1 RNA viral load (log10 copies/mL). Baseline value calculated as the average of pre-dose measurements collected at screening, randomization, and baseline visits.
Time Frame Baseline to Week 24 and Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS - as treated dual-tropic subjects. Discontinuations prior to time point of analysis imputed as 0.
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.
Overall Number of Participants Analyzed 57 52 58
Mean (Standard Error)
Unit of Measure: log10 copies/mL
Week 24 -0.850  (0.1510) -1.151  (0.1895) -0.926  (0.1679)
Week 48 -0.561  (0.1475) -1.066  (0.1962) -0.776  (0.1700)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments MVC QD vs PBO treatment difference at Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments TX difference adjusted for randomization strata.
Method of Estimation Estimation Parameter Least squares mean
Estimated Value 0.069
Confidence Interval (2-Sided) 95%
-0.396 to 0.535
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.2356
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments MVC BID vs PBO treatment difference at Week 24.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments TX difference adjusted for randomization strata.
Method of Estimation Estimation Parameter Least squares mean
Estimated Value -0.218
Confidence Interval (2-Sided) 95%
-0.694 to 0.258
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.2413
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments MVC QD vs PBO treatment difference at Week 48.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments TX difference adjusted for randomization strata.
Method of Estimation Estimation Parameter Least squares mean
Estimated Value 0.209
Confidence Interval (2-Sided) 95%
-0.262 to 0.681
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.2388
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments MVC BID vs PBO treatment difference at Week 48.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments TX difference adjusted for randomization strata.
Method of Estimation Estimation Parameter Least squares mean
Estimated Value -0.284
Confidence Interval (2-Sided) 95%
-0.767 to 0.199
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.2445
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Number of Subjects Per Genotype and Phenotype at Baseline and at Time of Failure
Hide Description Number of subjects per genotype and phenotype (tests for presence of non CCR5-tropic HIV-1 and for resistance to reverse transcriptase, protease, and fusion inhibitors) at baseline and at time of failure through Week 48 visit. Sensitivity to drug categorized as 0-1, 2-4, >4; scores defined as 0=resistance, 1=sensitive or susceptible with higher number indicating greater sensitivity or susceptibility.
Time Frame Baseline through Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS-as treated dual-tropic subjects. Genotype and phenotype at screening and at time of failure were not summarized as planned.
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
11.Secondary Outcome
Title Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24)
Hide Description Number of subjects per Tropism status (CCR5 [R5], CXCR4 [X4], Dual Mixed [DM], or Non-reportable/Non-phenotypable [NR/NP]) at Screening (Scr) and at time of treatment failure (Tx fail). Treatment failure defined as insufficient clinical response. HIV-1 RNA viral load <500 copies/ml categorized as below lower limit of quantification (BLQ). Tropism may have been assessed at either the Screening or Baseline visit. The assessment for time of treatment failure is defined as the last on-treatment assessment.
Time Frame Screening through Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS-as treated; N=subjects with TX failure due to insufficient clinical response and who had a tropism assessment at Screening. Subjects with DC prior to timepoint not included; LOCF if no result (viral load too low for analysis).
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.
Overall Number of Participants Analyzed 35 24 24
Measure Type: Number
Unit of Measure: participants
Scr: X4, Tx fail: X4 1 1 1
Scr: X4, Tx fail: DM 1 1 0
Scr: DM, Tx fail: R5 1 0 4
Scr: DM, Tx fail: X4 12 12 2
Scr: DM, Tx fail: DM 19 9 16
Scr DM, Tx fail: NR/NP 0 0 1
Scr DM, Tx fail: BLQ 1 0 0
Scr NR/NP, Tx fail: NR/NP 0 1 0
12.Secondary Outcome
Title Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48)
Hide Description Number of subjects per Tropism status (CCR5 [R5], CXCR4 [X4], Dual Mixed [DM], or Non-reportable/Non-phenotypable [NR/NP]) at Screening (Scr) and at time of treatment failure (Tx fail). Treatment failure defined as insufficient clinical response. HIV-1 RNA viral load <500 copies/ml categorized as below lower limit of quantification (BLQ). Tropism may have been assessed at either the Screening or Baseline visit. The assessment for time of treatment failure is defined as the last on-treatment assessment.
Time Frame Screening through Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS-as treated; N=subjects with TX failure due to insufficient clinical response and who had a tropism assessment at Screening. Subjects with DC prior to timepoint not included; LOCF if no result (viral load too low for analysis).
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.
Overall Number of Participants Analyzed 40 27 27
Measure Type: Number
Unit of Measure: participants
Scr: X4, Tx fail: X4 1 1 1
Scr: X4, Tx fail: DM 1 1 0
Scr: DM, Tx fail: R5 1 1 5
Scr: DM, Tx fail: X4 12 12 2
Scr: DM, Tx fail: DM 24 10 18
Scr: DM, Tx fail: NR/NP 0 1 1
Scr: DM, Tx fail: BLQ 1 0 0
Scr: NR/NP, Tx fail: NR/NP 0 1 0
13.Secondary Outcome
Title Number of Subjects With Treatment Failure at Week 24 by Overall Susceptibility Score (OSS) at Screening
Hide Description Number of subjects for association between screening resistance and virologic response as determined by treatment failure and OSS at screening. OSS categorized as 0-1, 2-4, >4 (maximum value of 6) and calculated as the sum of the net assessment of in vitro phenotypic and genotypic susceptibility using a binary scoring system (0= reduced susceptibility, 1=susceptible) for each antiretroviral agent in OBT. Higher scores indicate greater susceptibility.
Time Frame Screening, Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS - as treated dual-tropic subjects. Missing values imputed as LOCF.
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.
Overall Number of Participants Analyzed 57 52 58
Measure Type: Number
Unit of Measure: participants
Scr score: 0-1 21 12 17
Scr score: 2-4 35 35 40
Scr score: missing 1 1 1
14.Secondary Outcome
Title Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening
Hide Description Number of subjects for association between screening resistance and virologic response as determined by treatment failure and OSS at screening. OSS categorized as 0, 1, 2, or ≥3 (maximum value of 6) and calculated as the sum of the net assessment of in vitro phenotypic and genotypic susceptibility using a binary scoring system (0= reduced susceptibility, 1=susceptible) for each antiretroviral agent in OBT. Higher scores indicate greater susceptibility.
Time Frame Screening, Week48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS - as treated dual-tropic subjects. Missing values imputed as LOCF.
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.
Overall Number of Participants Analyzed 57 52 58
Measure Type: Number
Unit of Measure: particpants
Scr score: 0 1 2 2
Scr score: 1 19 11 15
Scr score: 2 21 14 13
Scr score: ≥3 15 24 27
Scr score: missing 1 1 1
15.Secondary Outcome
Title Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24)
Hide Description Number of subjects with AIDS-defining opportunistic illnesses based on investigator classification guided by a predefined list of clinical Category C Adverse Events per Center for Disease Control (CDC) HIV Classification System. Includes events occurring up to 7 days after last dose of study drug.
Time Frame Baseline through Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS - as randomized; N=number of subjects with Category C Adverse Events for maraviroc QD, maraviroc BID, and placebo, respectively. Week 48 results reflect subsequent updates to data originally reported at Week 24.
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.
Overall Number of Participants Analyzed 63 61 62
Measure Type: Number
Unit of Measure: participants
Candidiasis 0 0 1
Cytomegalovirus chorioretinitis 1 0 0
Herpes simplex 1 0 0
Histoplasmosis 1 0 0
Mycobacterium avium complex infection 1 0 0
Oesophageal candidiasis 0 2 0
Pneumocystis jiroveci pneumonia 3 1 0
Pneumonia 0 0 1
Encephalitis 0 0 1
16.Secondary Outcome
Title Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48)
Hide Description Number of subjects with AIDS-defining opportunistic illnesses based on investigator classification guided by a predefined list of clinical Category C Adverse Events per CDC HIV Classification System. Includes events occurring up to 7 days after last dose of study drug.
Time Frame Baseline through Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS - as randomized; N=number of subjects with Category C Adverse Events for maraviroc QD, maraviroc BID, and placebo, respectively. Week 48 results reflect subsequent updates to data originally reported at Week 24.
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.
Overall Number of Participants Analyzed 63 61 62
Measure Type: Number
Unit of Measure: participants
Candidiasis 0 1 1
Cytomegalovirus chorioretinitis 1 0 0
Histoplasmosis 1 0 0
Oesophageal candidiasis 0 2 0
Pneumococcal Sepsis 0 1 0
Pneumocystis jiroveci pneumonia 3 0 0
Pneumonia 0 1 0
Encephalitis 0 0 1
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening. Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening. Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.
All-Cause Mortality
Maraviroc QD Maraviroc BID Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Maraviroc QD Maraviroc BID Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   13/63 (20.63%)   14/62 (22.58%)   13/61 (21.31%) 
Blood and lymphatic system disorders       
Anaemia  1  1/63 (1.59%)  0/62 (0.00%)  0/61 (0.00%) 
Lymphadenitis  1  0/63 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Neutropenia  1  1/63 (1.59%)  0/62 (0.00%)  1/61 (1.64%) 
Cardiac disorders       
Myocardial infarction  1  0/63 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Gastrointestinal disorders       
Ascites  1  0/63 (0.00%)  0/62 (0.00%)  1/61 (1.64%) 
Diarrhoea  1  0/63 (0.00%)  1/62 (1.61%)  1/61 (1.64%) 
Pancreatitis acute  1  1/63 (1.59%)  0/62 (0.00%)  0/61 (0.00%) 
General disorders       
Asthenia  1  0/63 (0.00%)  1/62 (1.61%)  1/61 (1.64%) 
Condition aggravated  1  0/63 (0.00%)  0/62 (0.00%)  1/61 (1.64%) 
Disease progression  1  0/63 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Fatigue  1  0/63 (0.00%)  0/62 (0.00%)  1/61 (1.64%) 
Pyrexia  1  3/63 (4.76%)  1/62 (1.61%)  0/61 (0.00%) 
Hepatobiliary disorders       
Hepatitis  1  1/63 (1.59%)  0/62 (0.00%)  0/61 (0.00%) 
Immune system disorders       
Hypersensitivity  1  0/63 (0.00%)  1/62 (1.61%)  1/61 (1.64%) 
Infections and infestations       
Abscess  1  0/63 (0.00%)  0/62 (0.00%)  1/61 (1.64%) 
Bronchitis bacterial  1  0/63 (0.00%)  0/62 (0.00%)  1/61 (1.64%) 
Candidiasis  1  0/63 (0.00%)  0/62 (0.00%)  1/61 (1.64%) 
Clostridial infection  1  0/63 (0.00%)  2/62 (3.23%)  0/61 (0.00%) 
Ear infection  1  0/63 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Gastroenteritis viral  1  0/63 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Histoplasmosis  1  1/63 (1.59%)  0/62 (0.00%)  0/61 (0.00%) 
Lobar pneumonia  1  0/63 (0.00%)  0/62 (0.00%)  1/61 (1.64%) 
Meningitis aseptic  1  1/63 (1.59%)  0/62 (0.00%)  0/61 (0.00%) 
Oesophageal candidiasis  1  0/63 (0.00%)  2/62 (3.23%)  0/61 (0.00%) 
Pneumococcal sepsis  1  0/63 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Pneumocystis jiroveci pneumonia  1  3/63 (4.76%)  0/62 (0.00%)  0/61 (0.00%) 
Pneumonia  1  3/63 (4.76%)  2/62 (3.23%)  1/61 (1.64%) 
Pneumonia bacterial  1  1/63 (1.59%)  0/62 (0.00%)  0/61 (0.00%) 
Staphylococcal abscess  1  0/63 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Staphylococcal bacteraemia  1  1/63 (1.59%)  0/62 (0.00%)  0/61 (0.00%) 
Staphylococcal infection  1  0/63 (0.00%)  1/62 (1.61%)  1/61 (1.64%) 
Subcutaneous abscess  1  0/63 (0.00%)  0/62 (0.00%)  1/61 (1.64%) 
Urinary tract infection  1  0/63 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Injury, poisoning and procedural complications       
Humerus fracture  1  0/63 (0.00%)  0/62 (0.00%)  1/61 (1.64%) 
Metabolism and nutrition disorders       
Anorexia  1  0/63 (0.00%)  0/62 (0.00%)  1/61 (1.64%) 
Dehydration  1  0/63 (0.00%)  1/62 (1.61%)  1/61 (1.64%) 
Diabetes mellitus  1  1/63 (1.59%)  0/62 (0.00%)  0/61 (0.00%) 
Hypoglycaemia  1  1/63 (1.59%)  0/62 (0.00%)  0/61 (0.00%) 
Musculoskeletal and connective tissue disorders       
Pain in extremity  1  1/63 (1.59%)  0/62 (0.00%)  0/61 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
B-cell lymphoma  1  0/63 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Burkitt’s lymphoma  1  1/63 (1.59%)  0/62 (0.00%)  0/61 (0.00%) 
Lung adenocarcinoma  1  1/63 (1.59%)  0/62 (0.00%)  0/61 (0.00%) 
Nervous system disorders       
Central nervous system lesion  1  0/63 (0.00%)  0/62 (0.00%)  1/61 (1.64%) 
Encephalitis  1  0/63 (0.00%)  0/62 (0.00%)  1/61 (1.64%) 
Movement disorder  1  1/63 (1.59%)  0/62 (0.00%)  0/61 (0.00%) 
Pregnancy, puerperium and perinatal conditions       
Abortion spontaneous  1  0/63 (0.00%)  0/62 (0.00%)  1/61 (1.64%) 
Pregnancy  1  0/63 (0.00%)  0/62 (0.00%)  1/61 (1.64%) 
Psychiatric disorders       
Depression  1  0/63 (0.00%)  0/62 (0.00%)  2/61 (3.28%) 
Suicidal ideation  1  0/63 (0.00%)  0/62 (0.00%)  1/61 (1.64%) 
Renal and urinary disorders       
Nephrolithiasis  1  1/63 (1.59%)  0/62 (0.00%)  0/61 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  1/63 (1.59%)  0/62 (0.00%)  0/61 (0.00%) 
Dyspnoea  1  1/63 (1.59%)  0/62 (0.00%)  0/61 (0.00%) 
Haemothorax  1  0/63 (0.00%)  0/62 (0.00%)  1/61 (1.64%) 
Pleural effusion  1  0/63 (0.00%)  0/62 (0.00%)  1/61 (1.64%) 
Skin and subcutaneous tissue disorders       
Rash  1  0/63 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Maraviroc QD Maraviroc BID Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   46/63 (73.02%)   51/62 (82.26%)   42/61 (68.85%) 
Blood and lymphatic system disorders       
Anaemia  1  4/63 (6.35%)  0/62 (0.00%)  1/61 (1.64%) 
Gastrointestinal disorders       
Constipation  1  6/63 (9.52%)  5/62 (8.06%)  1/61 (1.64%) 
Diarrhoea  1  18/63 (28.57%)  12/62 (19.35%)  13/61 (21.31%) 
Nausea  1  9/63 (14.29%)  8/62 (12.90%)  12/61 (19.67%) 
Vomiting  1  8/63 (12.70%)  3/62 (4.84%)  8/61 (13.11%) 
General disorders       
Asthenia  1  0/63 (0.00%)  2/62 (3.23%)  7/61 (11.48%) 
Fatigue  1  8/63 (12.70%)  10/62 (16.13%)  11/61 (18.03%) 
Injection site reaction  1  7/63 (11.11%)  13/62 (20.97%)  9/61 (14.75%) 
Pyrexia  1  5/63 (7.94%)  6/62 (9.68%)  4/61 (6.56%) 
Infections and infestations       
Bronchitis  1  4/63 (6.35%)  6/62 (9.68%)  2/61 (3.28%) 
Herpes simplex  1  4/63 (6.35%)  4/62 (6.45%)  2/61 (3.28%) 
Influenza  1  1/63 (1.59%)  4/62 (6.45%)  1/61 (1.64%) 
Nasopharyngitis  1  5/63 (7.94%)  3/62 (4.84%)  3/61 (4.92%) 
Oral candidiasis  1  1/63 (1.59%)  5/62 (8.06%)  0/61 (0.00%) 
Pharyngitis  1  1/63 (1.59%)  5/62 (8.06%)  0/61 (0.00%) 
Sinusitis  1  3/63 (4.76%)  6/62 (9.68%)  4/61 (6.56%) 
Upper respiratory tract infection  1  5/63 (7.94%)  10/62 (16.13%)  5/61 (8.20%) 
Investigations       
Weight increased  1  4/63 (6.35%)  0/62 (0.00%)  0/61 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  3/63 (4.76%)  4/62 (6.45%)  1/61 (1.64%) 
Back pain  1  5/63 (7.94%)  8/62 (12.90%)  2/61 (3.28%) 
Pain in extremity  1  0/63 (0.00%)  6/62 (9.68%)  2/61 (3.28%) 
Nervous system disorders       
Dizziness  1  6/63 (9.52%)  6/62 (9.68%)  3/61 (4.92%) 
Headache  1  13/63 (20.63%)  11/62 (17.74%)  5/61 (8.20%) 
Psychiatric disorders       
Insomnia  1  5/63 (7.94%)  5/62 (8.06%)  3/61 (4.92%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  7/63 (11.11%)  6/62 (9.68%)  4/61 (6.56%) 
Oropharyngeal pain  1  3/63 (4.76%)  4/62 (6.45%)  1/61 (1.64%) 
Rhinorrhoea  1  0/63 (0.00%)  4/62 (6.45%)  0/61 (0.00%) 
Skin and subcutaneous tissue disorders       
Night sweats  1  4/63 (6.35%)  3/62 (4.84%)  1/61 (1.64%) 
Pruritus  1  2/63 (3.17%)  3/62 (4.84%)  5/61 (8.20%) 
Rash  1  7/63 (11.11%)  6/62 (9.68%)  7/61 (11.48%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.0)
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.
Pfizer has the right to review disclosures, requesting a delay of < 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), < 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier: NCT00098748     History of Changes
Other Study ID Numbers: A4001029
First Submitted: December 7, 2004
First Posted: December 8, 2004
Results First Submitted: March 25, 2010
Results First Posted: October 21, 2010
Last Update Posted: December 7, 2010