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    Clinical Trial Results:
    A multicentre, randomised, double-blind, placebo-controlled trial of novel CCR5 antagonist, UK-427,857, in comination with optimised background therapy versus optimised background therapy alone for the treatment of antiretroviral-experienced, non CCR5-tropic and HIV-1 infected subjects

    Summary
    EudraCT number
    		 2004-001779-20
    Trial protocol
    		 SE   DE   ES   BE   GB  
    Global end of trial date
    07 Apr 2009

    Results information
    Results version number
    		 v1(current)
    This version publication date
    01 Apr 2016
    First version publication date
    23 Jul 2015
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    A4001029
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00098748
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Pfizer Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    05 Mar 2007
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Apr 2009
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To confirm that the hypothesis that UK-427,857 added to Optimised Background Therapy (OBT) provides an additional reduction in plasma HIV-1 RNA (Human immunodeficiency virus-1 Ribonucleic Acid) compared to OBT alone, as measured by the difference between each of the two UK-427,857 regimens versus the placebo regimen in the mean changes from baseline in plasma HIV-1 RNA at week 24.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed
    Background therapy
    		 Subjects must have had greater than or equal to (≥3) months of prior treatment with at least 1 agent from 3 of the 4 antiretroviral drug classes.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    30 Nov 2004
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 11
    Country: Number of subjects enrolled
    United States: 125
    Country: Number of subjects enrolled
    Switzerland: 1
    Country: Number of subjects enrolled
    Netherlands: 1
    Country: Number of subjects enrolled
    Canada: 15
    Country: Number of subjects enrolled
    Spain: 9
    Country: Number of subjects enrolled
    United Kingdom: 6
    Country: Number of subjects enrolled
    Belgium: 11
    Country: Number of subjects enrolled
    Germany: 7
    Worldwide total number of subjects
    186
    EEA total number of subjects
    34
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    4
    Adults (18-64 years)
    181
    From 65 to 84 years
    1
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Total 232 subjects were screened of whom 190 were randomised to receive treatment from 05 March 2007 to 07 Apr 2009 in 72 centres in 9 countries. Four subjects were randomised, but not treated.

    Period 1
    Period 1 title
    Assigned to Study Treatment
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Maraviroc QD
    Arm description
    		 Maraviroc in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg = maraviroc placebo in the morning and active maraviroc in the evening.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Maraviroc
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received Maraviroc 150 mg QD.

    Arm title
    		 Maraviroc BID
    Arm description
    		 Maraviroc in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg twice a day (BID) arm = active drug in the morning and evening.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Maraviroc
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received Maraviroc 150 mg BID.

    Arm title
    		 Placebo
    Arm description
    		 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.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received Placebo matching to Maraviroc BID .

    Number of subjects in period 1
    		Maraviroc QD Maraviroc BID Placebo
    Started
    63
    63
    64
    Completed
    63
    61
    62
    Not completed
    0
    2
    2
         Randomized, but not treated
    -
    2
    2
    Period 2
    Period 2 title
    Received Study Treatment
    Is this the baseline period?
    		 Yes [1]
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Maraviroc QD
    Arm description
    		 Maraviroc in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg = maraviroc placebo in the morning and active maraviroc in the evening. Dual-tropic: Virus capable of using both CCR5 and CXCR4 coreceptors for cell entry.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Maraviroc
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received Maraviroc 150 mg QD.

    Arm title
    		 Maraviroc BID
    Arm description
    		 Maraviroc in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg twice a day (BID) arm = active drug in the morning and evening. Due to 1 placebo subject switched to maraviroc BID, BID = 62 subjects in Adverse event tables.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Maraviroc
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received Maraviroc 150 mg BID in combination with OBT.

    Arm title
    		 Placebo
    Arm description
    		 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. Due to 1 placebo subject switched to maraviroc BID, Placebo = 61 subjects in Adverse event tables.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received placebo matching to Maraviroc BID in combination with OBT.

    Notes
    [1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
    Justification: Period 2 is the baseline period, since baseline data represents only the subjects who received treatment.
    Number of subjects in period 2
    		Maraviroc QD Maraviroc BID Placebo
    Started
    63
    61
    62
    Dual-tropic Subjects by Phenotype Assay
    57
    52
    58
    Completed
    15
    25
    18
    Not completed
    48
    36
    44
         Death
    2
    1
    2
         Adverse event
    1
    2
    5
         Unspecified
    2
    2
    6
         Lack of efficacy
    40
    27
    27
         Subject defaulted
    3
    4
    4
    Period 3
    Period 3 title
    Continued on Open-Label Treatment
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Maraviroc QD
    Arm description
    		 Maraviroc in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg = maraviroc placebo in the morning and active maraviroc in the evening.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Maraviroc
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received Maraviroc 150 mg QD.

    Arm title
    		 Maraviroc BID
    Arm description
    		 Maraviroc 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.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Maraviroc
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received Maraviroc 150 mg BID in combination with OBT.

    Number of subjects in period 3 [2]
    		Maraviroc QD Maraviroc BID
    Started
    15
    25
    Completed
    7
    10
    Not completed
    8
    15
         Consent withdrawn by subject
    -
    4
         Other reason includes protocol violation
    6
    7
         Adverse event
    -
    1
         Lost to follow-up
    1
    1
         Lack of efficacy
    1
    2
    Notes
    [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Subjects in placebo group did not received open-label maraviroc due to study failing to reach its primary endpoint at Week 24.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Maraviroc QD
    Reporting group description
    		 Maraviroc in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg = maraviroc placebo in the morning and active maraviroc in the evening. Dual-tropic: Virus capable of using both CCR5 and CXCR4 coreceptors for cell entry.

    Reporting group title
    Maraviroc BID
    Reporting group description
    		 Maraviroc in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg twice a day (BID) arm = active drug in the morning and evening. Due to 1 placebo subject switched to maraviroc BID, BID = 62 subjects in Adverse event tables.

    Reporting group title
    Placebo
    Reporting group description
    		 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. Due to 1 placebo subject switched to maraviroc BID, Placebo = 61 subjects in Adverse event tables.

    Reporting group values
    		 Maraviroc QD Maraviroc BID Placebo Total
    Number of subjects
    		 63 61 62 186
    Age categorical
    Units: Subjects
        <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
    Units: years
        arithmetic mean (full range (min-max))
    		 42.7 (16 to 59) 42.5 (16 to 62) 44.6 (23 to 65) -
    Gender categorical
    Units: Subjects
        Female
    		 10 6 9 25
        Male
    		 53 55 53 161

    End points

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    End points reporting groups
    Reporting group title
    Maraviroc QD
    Reporting group description
    		 Maraviroc in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg = maraviroc placebo in the morning and active maraviroc in the evening.

    Reporting group title
    Maraviroc BID
    Reporting group description
    		 Maraviroc in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg twice a day (BID) arm = active drug in the morning and evening.

    Reporting group title
    Placebo
    Reporting group description
    		 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.
    Reporting group title
    Maraviroc QD
    Reporting group description
    		 Maraviroc in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg = maraviroc placebo in the morning and active maraviroc in the evening. Dual-tropic: Virus capable of using both CCR5 and CXCR4 coreceptors for cell entry.

    Reporting group title
    Maraviroc BID
    Reporting group description
    		 Maraviroc in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg twice a day (BID) arm = active drug in the morning and evening. Due to 1 placebo subject switched to maraviroc BID, BID = 62 subjects in Adverse event tables.

    Reporting group title
    Placebo
    Reporting group description
    		 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. Due to 1 placebo subject switched to maraviroc BID, Placebo = 61 subjects in Adverse event tables.
    Reporting group title
    Maraviroc QD
    Reporting group description
    		 Maraviroc in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg = maraviroc placebo in the morning and active maraviroc in the evening.

    Reporting group title
    Maraviroc BID
    Reporting group description
    		 Maraviroc 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.

    Primary: Change From Baseline in Human Immunodeficiency Virus (HIV-1) Viral Load (Ribonucleic Acid [RNA])

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    End point title
    		 Change From Baseline in Human Immunodeficiency Virus (HIV-1) Viral Load (Ribonucleic Acid [RNA])
    End point 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.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).
    End point type
    Primary
    End point timeframe
    Baseline to Week 24 and Week 48
    End point values
    		 Maraviroc QD Maraviroc BID Placebo
    Number of subjects analysed
    57
    52
    58
    Units: log10 copies/mL
    arithmetic mean (standard error)
        Week 24
    -0.89 ( 0.1706 )
    -1.194 ( 0.206 )
    -0.953 ( 0.1795 )
        Week 48
    -0.604 ( 0.1596 )
    -1.105 ( 0.2071 )
    0.839 ( 0.1851 )
    Statistical analysis title
    		 Maraviroc QD vs. Placebo at Week 24
    Statistical analysis description
    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.
    Comparison groups
    Maraviroc QD v Placebo
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 other [1]
    Method
    		 ANCOVA
    Parameter type
    		 Least squares mean
    Point estimate
    0.055
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 -0.528
         upper limit
    		 0.638
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2575
    Notes
    [1] - 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 non inferiority was tested. If upper bound of CI is <0.25 log10 copies/mL, noninferiority of MVC regimen to placebo was claimed.
    Statistical analysis title
    		 Maraviroc BID vs. Placebo at Week 24
    Statistical analysis description
    MVC BID vs PBO treatment difference at Week 24. TX difference adjusted for randomization strata. Bonferroni adjustment for multiple comparisons by use of 2-sided 97.5% CI to maintain alpha=0.05. Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.
    Comparison groups
    Maraviroc BID v Placebo
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANCOVA
    Parameter type
    		 Least squares mean
    Point estimate
    -0.232
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 -0.829
         upper limit
    		 0.364
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2637
    Statistical analysis title
    		 Maraviroc QD vs. Placebo at Week 48
    Statistical analysis description
    MVC QD vs PBO treatment difference at Week 48. TX difference adjusted for randomization strata. Bonferroni adjustment for multiple comparisons by use of 2-sided 97.5% CI to maintain alpha=0.05. Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.
    Comparison groups
    Maraviroc QD v Placebo
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANCOVA
    Parameter type
    		 Least squares mean
    Point estimate
    0.229
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 -0.351
         upper limit
    		 0.81
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2567
    Statistical analysis title
    		 Maraviroc BID vs. Placebo at Week 48
    Statistical analysis description
    MVC BID vs PBO treatment difference at Week 48. TX difference adjusted for randomization strata. Bonferroni adjustment for multiple comparisons by use of 2-sided 97.5% CI to maintain alpha=0.05. Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.
    Comparison groups
    Maraviroc BID v Placebo
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANCOVA
    Parameter type
    		 Least squares mean
    Point estimate
    -0.261
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 -0.856
         upper limit
    		 0.333
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2628

    Secondary: Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL

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    End point title
    		 Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL
    End point description
    FAS - as treated dual-tropic subjects. Missing values counted as failures/non-responders (counted as not achieving the stated criterion).
    End point type
    Secondary
    End point timeframe
    Week 24, Week 48
    End point values
    		 Maraviroc QD Maraviroc BID Placebo
    Number of subjects analysed
    57
    52
    58
    Units: subjects
        Week 24
    14
    16
    14
        Week 48
    12
    16
    13
    Statistical analysis title
    		 Maraviroc QD vs. Placebo at Week 24
    Statistical analysis description
    MVC QD vs PBO treatment difference in proportions at Week 24. 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.
    Comparison groups
    Placebo v Maraviroc QD
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 difference in proportions
    Point estimate
    0.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.12
         upper limit
    		 0.18
    Statistical analysis title
    		 Maraviroc BID vs. Placebo at Week 24
    Statistical analysis description
    MVC BID vs PBO treatment difference in proportions at Week 24. 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.
    Comparison groups
    Maraviroc BID v Placebo
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 difference in proportions
    Point estimate
    0.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.08
         upper limit
    		 0.23
    Statistical analysis title
    		 Maraviroc QD vs. Placebo at Week 48
    Statistical analysis description
    MVC QD vs PBO treatment difference in proportions at Week 48. 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.
    Comparison groups
    Maraviroc QD v Placebo
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 difference in proportions
    Point estimate
    0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.12
         upper limit
    		 0.17
    Statistical analysis title
    		 Maraviroc BID vs. Placebo at Week 48
    Statistical analysis description
    MVC BID vs PBO treatment difference in proportions at Week 48. 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.
    Comparison groups
    Maraviroc BID v Placebo
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 difference in proportions
    Point estimate
    0.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.07
         upper limit
    		 0.25

    Secondary: 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

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    End point 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
    End point 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.FAS-as treated dual-tropic subjects. Missing values counted as failures/non-responders (counted as not achieving the stated criterion).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24, Week 48
    End point values
    		 Maraviroc QD Maraviroc BID Placebo
    Number of subjects analysed
    57
    52
    58
    Units: subjects
        Week 24
    24
    25
    23
        Week 48
    14
    22
    18
    Statistical analysis title
    		 Maraviroc QD vs. Placebo at Week 24
    Statistical analysis description
    MVC QD vs PBO treatment difference in proportions at Week 24. 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.
    Comparison groups
    Maraviroc QD v Placebo
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 difference in proportions
    Point estimate
    0.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.15
         upper limit
    		 0.2
    Statistical analysis title
    		 Maraviroc BID vs. Placebo at Week 24
    Statistical analysis description
    MVC BID vs PBO treatment difference in proportions at Week 24. 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.
    Comparison groups
    Maraviroc BID v Placebo
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 difference in proportions
    Point estimate
    0.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.1
         upper limit
    		 0.26
    Statistical analysis title
    		 Maraviroc QD vs. Placebo at Week 48
    Statistical analysis description
    MVC QD vs PBO treatment difference in proportions at Week 48. 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.
    Comparison groups
    Maraviroc QD v Placebo
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 difference in proportions
    Point estimate
    -0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.22
         upper limit
    		 0.1
    Statistical analysis title
    		 Maraviroc BID vs. Placebo at Week 48
    Statistical analysis description
    MVC BID vs PBO treatment difference in proportions at Week 48. 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.
    Comparison groups
    Maraviroc BID v Placebo
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 difference in proportions
    Point estimate
    0.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.07
         upper limit
    		 0.28

    Secondary: 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

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    End point 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
    End point 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. FAS-as treated dual-tropic subjects. Missing values counted as failures/non-responders (counted as not achieving the stated criterion).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24, Week 48
    End point values
    		 Maraviroc QD Maraviroc BID Placebo
    Number of subjects analysed
    57
    52
    58
    Units: subjects
        Week 24
    18
    23
    21
        Week 48
    13
    20
    15
    Statistical analysis title
    		 Maraviroc QD vs. Placebo at Week 24
    Statistical analysis description
    MVC QD vs PBO treatment difference in proportions at Week 24. 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.
    Comparison groups
    Maraviroc QD v Placebo
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 difference in proportions
    Point estimate
    -0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.21
         upper limit
    		 0.12
    Statistical analysis title
    		 Maraviroc BID vs. Placebo at Week 24
    Statistical analysis description
    MVC BID vs PBO treatment difference in proportions at Week 24. 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.
    Comparison groups
    Maraviroc BID v Placebo
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 difference in proportions
    Point estimate
    0.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.1
         upper limit
    		 0.26
    Statistical analysis title
    		 Maraviroc QD vs. Placebo at Week 48
    Statistical analysis description
    MVC QD vs PBO treatment difference in proportions at Week 48. 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.
    Comparison groups
    Maraviroc QD v Placebo
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 difference in proportions
    Point estimate
    -0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.18
         upper limit
    		 0.13
    Statistical analysis title
    		 Maraviroc BID vs. Placebo at Week 48
    Statistical analysis description
    MVC BID vs PBO treatment difference in proportions at Week 48. 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.
    Comparison groups
    Maraviroc BID v Placebo
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 difference in proportions
    Point estimate
    0.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.04
         upper limit
    		 0.29

    Secondary: Number of Subjects With HIV-1 RNA Levels < 50 Copies/mL

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    End point title
    		 Number of Subjects With HIV-1 RNA Levels < 50 Copies/mL
    End point description
    FAS - as treated dual-tropic subjects. Missing values counted as failures/non-responders (counted as not achieving the stated criterion).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24, Week 48
    End point values
    		 Maraviroc QD Maraviroc BID Placebo
    Number of subjects analysed
    57
    52
    58
    Units: subjects
        Week 24
    12
    14
    9
        Week 48
    10
    14
    13
    Statistical analysis title
    		 Maraviroc QD vs. Placebo at Week 24
    Statistical analysis description
    MVC QD vs PBO treatment difference in proportions at Week 24. 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.
    Comparison groups
    Maraviroc QD v Placebo
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 difference in proportions
    Point estimate
    0.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.07
         upper limit
    		 0.2
    Statistical analysis title
    		 Maraviroc BID vs. Placebo at Week 24
    Statistical analysis description
    MVC BID vs PBO difference in proportions at Week 24. 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.
    Comparison groups
    Maraviroc BID v Placebo
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 difference in proportions
    Point estimate
    0.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.03
         upper limit
    		 0.26
    Statistical analysis title
    		 Maraviroc QD vs. Placebo at Week 48
    Statistical analysis description
    MVC QD vs PBO treatment difference in proportions at Week 48. 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.
    Comparison groups
    Maraviroc QD v Placebo
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 difference in proportions
    Point estimate
    -0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.18
         upper limit
    		 0.1
    Statistical analysis title
    		 Maraviroc BID vs. Placebo at Week 48
    Statistical analysis description
    MVC BID vs PBO treatment difference in proportions at Week 48. 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.
    Comparison groups
    Maraviroc BID v Placebo
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 difference in proportions
    Point estimate
    0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.1
         upper limit
    		 0.21

    Secondary: Change From Baseline in CD4 Cell Count

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    End point title
    		 Change From Baseline in CD4 Cell Count
    End point 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. FAS - as treated dual-tropic subjects. Placebo N: 4 subjects did not have on-treatment information. Missing data imputed using LOCF.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 24 and Week 48
    End point values
    		 Maraviroc QD Maraviroc BID Placebo
    Number of subjects analysed
    57
    52
    54
    Units: cells/µL
    arithmetic mean (standard error)
        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 )
    Statistical analysis title
    		 Maraviroc QD vs. Placebo at Week 24
    Statistical analysis description
    MVC QD vs PBO treatment difference at Week 24. TX difference adjusted for randomization strata. Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.
    Comparison groups
    Maraviroc QD v Placebo
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANCOVA
    Parameter type
    		 Least squares mean
    Point estimate
    23.927
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.359
         upper limit
    		 49.213
    Variability estimate
    Standard error of the mean
    Dispersion value
    12.8025
    Statistical analysis title
    		 Maraviroc BID vs. Placebo at Week 24
    Statistical analysis description
    MVC BID vs PBO treatment difference at Week 24. TX difference adjusted for randomization strata. Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.
    Comparison groups
    Maraviroc BID v Placebo
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANCOVA
    Parameter type
    		 Least squares mean
    Point estimate
    26.679
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.869
         upper limit
    		 52.49
    Variability estimate
    Standard error of the mean
    Dispersion value
    13.0678
    Statistical analysis title
    		 Maraviroc QD vs. Placebo at Week 48
    Statistical analysis description
    MVC QD vs PBO treatment difference at Week 48. TX difference adjusted for randomization strata. Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.
    Comparison groups
    Maraviroc QD v Placebo
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANCOVA
    Parameter type
    		 Least squares mean
    Point estimate
    14.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17.8
         upper limit
    		 47.03
    Variability estimate
    Standard error of the mean
    Dispersion value
    16.412
    Statistical analysis title
    		 Maraviroc BID vs. Placebo at Week 48
    Statistical analysis description
    MVC BID vs PBO treatment difference at Week 48. TX difference adjusted for randomization strata. Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.
    Comparison groups
    Placebo v Maraviroc BID
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANCOVA
    Parameter type
    		 Least squares mean
    Point estimate
    27.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.38
         upper limit
    		 60.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    16.754

    Secondary: Change From Baseline in CD8 Cell Count

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    End point title
    		 Change From Baseline in CD8 Cell Count
    End point 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. FAS - as treated dual-tropic subjects. Placebo N: 4 subjects did not have on-treatment information. Missing data imputed using LOCF.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 24 and Week 48
    End point values
    		 Maraviroc QD Maraviroc BID Placebo
    Number of subjects analysed
    57
    52
    54
    Units: cells/µL
    arithmetic mean (standard error)
        Week 24
    391.061 ( 57.0135 )
    322.683 ( 68.3315 )
    154.293 ( 46.81 )
        Week 48
    351.23 ( 54.653 )
    342.87 ( 72.222 )
    192.3 ( 62.578 )
    Statistical analysis title
    		 Maraviroc QD vs. Placebo at Week 24
    Statistical analysis description
    MVC QD vs PBO treatment difference at Week 24. TX difference adjusted for randomization strata. Negative values for change from baseline= benefit of TX; negative values for MVC vs PBO=advantage of MVC. TX difference adjusted for randomization strata.
    Comparison groups
    Maraviroc QD v Placebo
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANCOVA
    Parameter type
    		 Least squares mean
    Point estimate
    234.499
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 74.913
         upper limit
    		 394.084
    Variability estimate
    Standard error of the mean
    Dispersion value
    80.799
    Statistical analysis title
    		 Maraviroc BID vs. Placebo at Week 24
    Statistical analysis description
    MVC BID vs PBO treatment difference at Week 24. TX difference adjusted for randomization strata. Negative values for change from baseline= benefit of TX; negative values for MVC vs PBO=advantage of MVC. TX difference adjusted for randomization strata.
    Comparison groups
    Maraviroc BID v Placebo
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANCOVA
    Parameter type
    		 Least squares mean
    Point estimate
    188.817
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 23.999
         upper limit
    		 353.635
    Variability estimate
    Standard error of the mean
    Dispersion value
    83.4484
    Statistical analysis title
    		 Maraviroc QD vs. Placebo at Week 48
    Statistical analysis description
    MVC QD vs PBO treatment difference at Week 48. TX difference adjusted for randomization strata. Negative values for change from baseline= benefit of TX; negative values for MVC vs PBO=advantage of MVC. TX difference adjusted for randomization strata.
    Comparison groups
    Maraviroc QD v Placebo
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANCOVA
    Parameter type
    		 Least squares mean
    Point estimate
    155.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.49
         upper limit
    		 328.37
    Variability estimate
    Standard error of the mean
    Dispersion value
    87.304
    Statistical analysis title
    		 Maraviroc BID vs. Placebo at Week 48
    Statistical analysis description
    MVC QD vs PBO treatment difference at Week 48. TX difference adjusted for randomization strata. Negative values for change from baseline= benefit of TX; negative values for MVC vs PBO=advantage of MVC. TX difference adjusted for randomization strata.
    Comparison groups
    Maraviroc BID v Placebo
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANCOVA
    Parameter type
    		 Least squares mean
    Point estimate
    182.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.81
         upper limit
    		 361.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    90.174

    Secondary: Time (50% Quartile Point Estimate) to Virologic Failure

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    End point title
    		 Time (50% Quartile Point Estimate) to Virologic Failure
    End point 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.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. Here, "99999" in the upper limit of confidence interval values signifies parameter not estimable (NA).
    End point type
    Secondary
    End point timeframe
    Day 1 through Week 24 and through Week 48
    End point values
    		 Maraviroc QD Maraviroc BID Placebo
    Number of subjects analysed
    57
    52
    58
    Units: days
    median (confidence interval 95%)
        Week 24 (n=35, 23, 29)
    88 (59 to 99999)
    189 (113 to 189)
    100 (60 to 99999)
        Week 48 (n=45, 37, 44)
    0 (0 to 0)
    0 (0 to 142)
    0 (0 to 29)
    Statistical analysis title
    		 Maraviroc QD vs. Placebo at Week 24
    Statistical analysis description
    MVC QD vs PBO at Week 24. Kaplan-Meier survival estimates. TX difference evaluated by log-rank test.
    Comparison groups
    Maraviroc QD v Placebo
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7524
    Method
    		 Logrank
    Confidence interval
    Statistical analysis title
    		 Maraviroc BID vs. Placebo at Week 24
    Statistical analysis description
    MVC BID vs PBO at Week 24. Kaplan-Meier survival estimates. TX difference evaluated by log-rank test.
    Comparison groups
    Maraviroc BID v Placebo
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.254
    Method
    		 Logrank
    Confidence interval
    Statistical analysis title
    		 Maraviroc QD vs. Placebo at Week 48
    Statistical analysis description
    MVC QD vs PBO at Week 48. Kaplan-Meier survival estimates. TX difference evaluated by log-rank test.
    Comparison groups
    Maraviroc QD v Placebo
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8243
    Method
    		 Logrank
    Confidence interval
    Statistical analysis title
    		 Maraviroc BID vs. Placebo at Week 48
    Statistical analysis description
    MVC BID vs PBO at Week 48. Kaplan-Meier survival estimates. TX difference evaluated by log-rank test.
    Comparison groups
    Maraviroc BID v Placebo
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6657
    Method
    		 Logrank
    Confidence interval

    Secondary: Change From Baseline in Time Averaged Difference (TAD) in log10 HIV-1 RNA

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    End point title
    		 Change From Baseline in Time Averaged Difference (TAD) in log10 HIV-1 RNA
    End point 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.FAS - as treated dual-tropic subjects. Discontinuations prior to time point of analysis imputed as 0.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 24 and Week 48
    End point values
    		 Maraviroc QD Maraviroc BID Placebo
    Number of subjects analysed
    57
    52
    58
    Units: log10 copies/mL
    arithmetic mean (standard error)
        Week 24
    -0.85 ( 0.151 )
    -1.151 ( 0.1895 )
    -0.926 ( 0.1679 )
        Week 48
    -0.561 ( 0.1475 )
    -1.066 ( 0.1962 )
    -0.776 ( 0.17 )
    Statistical analysis title
    		 Maraviroc QD vs. Placebo at Week 24
    Statistical analysis description
    MVC QD vs PBO treatment difference at Week 24. TX difference adjusted for randomization strata.
    Comparison groups
    Maraviroc QD v Placebo
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANCOVA
    Parameter type
    		 Least squares mean
    Point estimate
    0.069
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.396
         upper limit
    		 0.535
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2356
    Statistical analysis title
    		 Maraviroc BID vs. Placebo at Week 24
    Statistical analysis description
    MVC BID vs PBO treatment difference at Week 24. TX difference adjusted for randomization strata.
    Comparison groups
    Maraviroc BID v Placebo
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANCOVA
    Parameter type
    		 Least squares mean
    Point estimate
    -0.218
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.694
         upper limit
    		 0.258
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2413
    Statistical analysis title
    		 Maraviroc QD vs. Placebo at Week 48
    Statistical analysis description
    MVC QD vs PBO treatment difference at Week 48. TX difference adjusted for randomization strata.
    Comparison groups
    Maraviroc QD v Placebo
    Number of subjects included in analysis
    115
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANCOVA
    Parameter type
    		 Least squares mean
    Point estimate
    0.209
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.262
         upper limit
    		 0.681
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2388
    Statistical analysis title
    		 Maraviroc BID vs. Placebo at Week 48
    Statistical analysis description
    MVC BID vs PBO treatment difference at Week 48. TX difference adjusted for randomization strata.
    Comparison groups
    Maraviroc BID v Placebo
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 ANCOVA
    Parameter type
    		 Least squares mean
    Point estimate
    -0.284
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.767
         upper limit
    		 0.199
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2445

    Secondary: Number of Subjects Per Genotype and Phenotype at Baseline and at Time of Failure

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    End point title
    		 Number of Subjects Per Genotype and Phenotype at Baseline and at Time of Failure
    End point 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. FAS-as treated dual-tropic subjects. Genotype and phenotype at screening and at time of failure were not summarized as planned.
    End point type
    Secondary
    End point timeframe
    Baseline through Week 48
    End point values
    		 Maraviroc QD Maraviroc BID Placebo
    Number of subjects analysed
    0 [2]
    0 [3]
    0 [4]
    Units: subjects
    Notes
    [2] - Genotype and phenotype at screening and at time of failure were not summarized as planned.
    [3] - Genotype and phenotype at screening and at time of failure were not summarized as planned.
    [4] - Genotype and phenotype at screening and at time of failure were not summarized as planned.
    No statistical analyses for this end point

    Secondary: Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24)

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    End point title
    		 Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24)
    End point 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. Full Analysis Set-as treated; Subjects with DC prior to timepoint not included; LOCF if no result (viral load too low for analysis).
    End point type
    Secondary
    End point timeframe
    Screening through Week 24
    End point values
    		 Maraviroc QD Maraviroc BID Placebo
    Number of subjects analysed
    35 [5]
    24 [6]
    24 [7]
    Units: subjects
        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
    Notes
    [5] - Subjects with TX failure due to insufficient clinical response and had a tropism assessment.
    [6] - Subjects with TX failure due to insufficient clinical response and had a tropism assessment.
    [7] - Subjects with TX failure due to insufficient clinical response and had a tropism assessment.
    No statistical analyses for this end point

    Secondary: Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48)

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    End point title
    		 Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48)
    End point 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.Full Analysis Set-as treated Subjects with DC prior to timepoint not included; LOCF if no result (viral load too low for analysis).
    End point type
    Secondary
    End point timeframe
    Screening through Week 48
    End point values
    		 Maraviroc QD Maraviroc BID Placebo
    Number of subjects analysed
    40 [8]
    27 [9]
    27 [10]
    Units: subjects
        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
    Notes
    [8] - Subjects with TX failure due to insufficient clinical response and had a tropism assessment
    [9] - Subjects with TX failure due to insufficient clinical response and had a tropism assessment
    [10] - Subjects with TX failure due to insufficient clinical response and had a tropism assessment
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment Failure at Week 24 by Overall Susceptibility Score (OSS) at Screening

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    End point title
    		 Number of Subjects With Treatment Failure at Week 24 by Overall Susceptibility Score (OSS) at Screening
    End point 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. Full Analysis Set - as treated dual-tropic subjects. Missing values imputed as LOCF.
    End point type
    Secondary
    End point timeframe
    Screening, Week 24
    End point values
    		 Maraviroc QD Maraviroc BID Placebo
    Number of subjects analysed
    57
    52
    58
    Units: subjects
        Scr score: 0-1
    21
    12
    17
        Scr score: 2-4
    35
    35
    40
        Scr score: missing
    1
    1
    1
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening

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    End point title
    		 Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening
    End point 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. Full Analysis Set - as treated dual-tropic subjects. Missing values imputed as LOCF.
    End point type
    Secondary
    End point timeframe
    Screening, Week48
    End point values
    		 Maraviroc QD Maraviroc BID Placebo
    Number of subjects analysed
    57
    52
    58
    Units: subjects
        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
    No statistical analyses for this end point

    Secondary: Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24)

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    End point title
    		 Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24)
    End point 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. Full analysis set - as randomized. Week 48 results reflect subsequent updates to data originally reported at Week 24.
    End point type
    Secondary
    End point timeframe
    Baseline through Week 24
    End point values
    		 Maraviroc QD Maraviroc BID Placebo
    Number of subjects analysed
    63 [11]
    61 [12]
    62 [13]
    Units: subjects
        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
    Notes
    [11] - Number of subjects with Category C Adverse Events
    [12] - Number of subjects with Category C Adverse Events
    [13] - Number of subjects with Category C Adverse Events
    No statistical analyses for this end point

    Secondary: Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48)

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    End point title
    		 Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48)
    End point 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. Full Analysis Set - as randomized. Week 48 results reflect subsequent updates to data originally reported at Week 24.
    End point type
    Secondary
    End point timeframe
    Baseline through Week 48
    End point values
    		 Maraviroc QD Maraviroc BID Placebo
    Number of subjects analysed
    63 [14]
    61 [15]
    62 [16]
    Units: subjects
        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
    Notes
    [14] - Number of subjects with Category C Adverse Events
    [15] - Number of subjects with Category C Adverse Events
    [16] - Number of subjects with Category C Adverse Events
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    AEs/SAEs: recorded from Day 1 up to Week 48. All serious adverse events were reported up to 7 months after Week 48 regardless of duration of follow-up.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    Maraviroc QD
    Reporting 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 = maraviroc placebo in the morning and active maraviroc in the evening.

    Reporting group title
    Maraviroc BID
    Reporting group description
    		 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.

    Reporting group title
    Placebo
    Reporting group description
    		 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.

    Serious adverse events
    		 Maraviroc QD Maraviroc BID Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    13 / 63 (20.63%)
    14 / 62 (22.58%)
    13 / 61 (21.31%)
         number of deaths (all causes)
    2
    1
    2
         number of deaths resulting from adverse events
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    B-cell lymphoma
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Burkitt’s lymphoma
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pregnancy
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Condition aggravated
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Disease progression
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    3 / 63 (4.76%)
    1 / 62 (1.61%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemothorax
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    2 / 61 (3.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Humerus fracture
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Myocardial infarction
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Central nervous system lesion
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Movement disorder
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lymphadenitis
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Ascites
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatitis
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abscess
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis bacterial
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Candida infection
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 63 (0.00%)
    2 / 62 (3.23%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ear infection
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Encephalitis
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Histoplasmosis
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Meningitis aseptic
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophageal candidiasis
         subjects affected / exposed
    0 / 63 (0.00%)
    2 / 62 (3.23%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumococcal sepsis
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    3 / 63 (4.76%)
    0 / 62 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    3 / 63 (4.76%)
    2 / 62 (3.23%)
    2 / 61 (3.28%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal abscess
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Maraviroc QD Maraviroc BID Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    47 / 63 (74.60%)
    51 / 62 (82.26%)
    43 / 61 (70.49%)
    Investigations
    Weight increased
         subjects affected / exposed
    4 / 63 (6.35%)
    0 / 62 (0.00%)
    0 / 61 (0.00%)
         occurrences all number
    4
    0
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    6 / 63 (9.52%)
    7 / 62 (11.29%)
    3 / 61 (4.92%)
         occurrences all number
    6
    8
    3
    Headache
         subjects affected / exposed
    13 / 63 (20.63%)
    11 / 62 (17.74%)
    5 / 61 (8.20%)
         occurrences all number
    14
    15
    5
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    4 / 63 (6.35%)
    0 / 62 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    4
    0
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 63 (0.00%)
    2 / 62 (3.23%)
    7 / 61 (11.48%)
         occurrences all number
    0
    2
    7
    Fatigue
         subjects affected / exposed
    9 / 63 (14.29%)
    10 / 62 (16.13%)
    11 / 61 (18.03%)
         occurrences all number
    12
    12
    12
    Injection site reaction
         subjects affected / exposed
    7 / 63 (11.11%)
    13 / 62 (20.97%)
    9 / 61 (14.75%)
         occurrences all number
    8
    14
    9
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    6 / 63 (9.52%)
    5 / 62 (8.06%)
    1 / 61 (1.64%)
         occurrences all number
    6
    6
    1
    Diarrhoea
         subjects affected / exposed
    19 / 63 (30.16%)
    12 / 62 (19.35%)
    13 / 61 (21.31%)
         occurrences all number
    24
    13
    15
    Nausea
         subjects affected / exposed
    10 / 63 (15.87%)
    8 / 62 (12.90%)
    12 / 61 (19.67%)
         occurrences all number
    12
    8
    13
    Vomiting
         subjects affected / exposed
    8 / 63 (12.70%)
    3 / 62 (4.84%)
    8 / 61 (13.11%)
         occurrences all number
    9
    4
    9
    Reproductive system and breast disorders
    Metrorrhagia
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
    0 / 61 (0.00%)
         occurrences all number
    0
    1
    0
    Prostatitis
         subjects affected / exposed
    1 / 63 (1.59%)
    3 / 62 (4.84%)
    0 / 61 (0.00%)
         occurrences all number
    1
    3
    0
    Vulvovaginal pruritus
         subjects affected / exposed
    0 / 63 (0.00%)
    0 / 62 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    7 / 63 (11.11%)
    6 / 62 (9.68%)
    4 / 61 (6.56%)
         occurrences all number
    8
    6
    4
    Oropharyngeal pain
         subjects affected / exposed
    3 / 63 (4.76%)
    4 / 62 (6.45%)
    1 / 61 (1.64%)
         occurrences all number
    4
    5
    1
    Rhinorrhoea
         subjects affected / exposed
    0 / 63 (0.00%)
    4 / 62 (6.45%)
    0 / 61 (0.00%)
         occurrences all number
    0
    4
    0
    Skin and subcutaneous tissue disorders
    Night sweats
         subjects affected / exposed
    4 / 63 (6.35%)
    3 / 62 (4.84%)
    1 / 61 (1.64%)
         occurrences all number
    4
    3
    1
    Pruritus
         subjects affected / exposed
    2 / 63 (3.17%)
    3 / 62 (4.84%)
    5 / 61 (8.20%)
         occurrences all number
    3
    4
    8
    Rash
         subjects affected / exposed
    7 / 63 (11.11%)
    6 / 62 (9.68%)
    7 / 61 (11.48%)
         occurrences all number
    7
    6
    8
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    5 / 63 (7.94%)
    5 / 62 (8.06%)
    3 / 61 (4.92%)
         occurrences all number
    5
    5
    3
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    3 / 63 (4.76%)
    4 / 62 (6.45%)
    1 / 61 (1.64%)
         occurrences all number
    3
    4
    2
    Back pain
         subjects affected / exposed
    5 / 63 (7.94%)
    8 / 62 (12.90%)
    2 / 61 (3.28%)
         occurrences all number
    8
    9
    2
    Pain in extremity
         subjects affected / exposed
    0 / 63 (0.00%)
    6 / 62 (9.68%)
    2 / 61 (3.28%)
         occurrences all number
    0
    6
    2
    Infections and infestations
    Pyrexia
         subjects affected / exposed
    5 / 63 (7.94%)
    6 / 62 (9.68%)
    4 / 61 (6.56%)
         occurrences all number
    5
    6
    8
    Bronchitis
         subjects affected / exposed
    4 / 63 (6.35%)
    6 / 62 (9.68%)
    2 / 61 (3.28%)
         occurrences all number
    4
    6
    2
    Herpes simplex
         subjects affected / exposed
    2 / 63 (3.17%)
    4 / 62 (6.45%)
    2 / 61 (3.28%)
         occurrences all number
    4
    4
    2
    Influenza
         subjects affected / exposed
    1 / 63 (1.59%)
    4 / 62 (6.45%)
    1 / 61 (1.64%)
         occurrences all number
    1
    4
    1
    Nasopharyngitis
         subjects affected / exposed
    5 / 63 (7.94%)
    2 / 62 (3.23%)
    3 / 61 (4.92%)
         occurrences all number
    8
    2
    4
    Oral candidiasis
         subjects affected / exposed
    1 / 63 (1.59%)
    5 / 62 (8.06%)
    0 / 61 (0.00%)
         occurrences all number
    1
    5
    0
    Pharyngitis
         subjects affected / exposed
    1 / 63 (1.59%)
    5 / 62 (8.06%)
    0 / 61 (0.00%)
         occurrences all number
    1
    5
    0
    Sinusitis
         subjects affected / exposed
    3 / 63 (4.76%)
    6 / 62 (9.68%)
    4 / 61 (6.56%)
         occurrences all number
    4
    9
    4
    Upper respiratory tract infection
         subjects affected / exposed
    5 / 63 (7.94%)
    10 / 62 (16.13%)
    5 / 61 (8.20%)
         occurrences all number
    7
    16
    6
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 63 (1.59%)
    5 / 62 (8.06%)
    0 / 61 (0.00%)
         occurrences all number
    1
    5
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    09 Aug 2005
    1- Addition of pharmacokinetic data to support the suggested guidance for use of efavirenz with UK-427,857 alone. 2- Upon treatment failure, in addition to a confirmatory plasma HIV-1 RNA sample, the following shall also be collected: a.a plasma sample for HIV-1 co-receptor tropism phenotype as determined by the ViroLogic recombinant virus entry; b.a plasma sample for HIV-1 genotype and phenotype as determined by the ViroLogic PhenoSense GT assay;
    20 Jan 2006
    1- Addition of blood sample collection at the Randomization visit. 2- Exclusion of isoniazid use. 3- Exclusion of the initiation of potentially myelosuppressive, neurotoxic, hepatotoxic and/or cytotoxic agents within 60 days prior to randomization. 4- Removal of specific exclusion criteria pertaining to history of cardiovascular and cerebrovascular disease.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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