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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 HIV-1 Infected Subjects (MOTIVATE 1)

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ClinicalTrials.gov Identifier: NCT00098306
Recruitment Status : Completed
First Posted : December 7, 2004
Results First Posted : April 27, 2012
Last Update Posted : April 27, 2012
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
ViiV Healthcare

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition HIV Infections
Interventions Drug: Maraviroc (UK-427,857)
Drug: Optimized Background Therapy
Drug: Placebo
Enrollment 601
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Maraviroc QD, Double Blind Maraviroc BID, Double Blind Placebo, Double Blind Maraviroc BID, Open Label In Study-off Drug (ISOD), Open Label Maraviroc BID, Observation Phase In Study-off Drug (ISOD), Observation Phase
Hide Arm/Group Description Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning. Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Participants from maraviroc QD, maraviroc BID and Placebo (double blind phase) who received maraviroc 150 or 300 mg BID in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) during open label phase. Participants from maraviroc QD, maraviroc BID and Placebo (double blind phase) who received no study treatment along with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) in during open label phase. Participants continuing from open label phase, who received maraviroc 150 or 300 mg BID in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) during observational phase. Participants continuing from open label phase, who received no study treatment along with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) during observational phase.
Period Title: Double Blind
Started 241 240 120 0 0 0 0
Treated 232 235 118 0 0 0 0
Completed 0 0 0 0 0 0 0
Not Completed 241 240 120 0 0 0 0
Reason Not Completed
Randomized, not treated             9             5             2             0             0             0             0
Ongoing at cut-off date             151             166             72             0             0             0             0
Adverse Event             11             10             6             0             0             0             0
Lack of Efficacy             43             34             17             0             0             0             0
Death             1             4             1             0             0             0             0
Participant defaulted             19             18             11             0             0             0             0
Un-specified             7             3             11             0             0             0             0
Period Title: Open Label
Started 0 0 0 327 62 0 0
Completed 0 0 0 0 0 0 0
Not Completed 0 0 0 327 62 0 0
Reason Not Completed
Lack of Efficacy             0             0             0             13             0             0             0
Adverse Event             0             0             0             2             0             0             0
Death             0             0             0             4             0             0             0
Participant defaulted             0             0             0             24             0             0             0
Un-specified             0             0             0             15             0             0             0
Ongoing at cut-off date             0             0             0             269             62             0             0
Period Title: Observational Phase
Started 0 0 0 0 0 250 81
Completed 0 0 0 0 0 204 55
Not Completed 0 0 0 0 0 46 26
Reason Not Completed
Death             0             0             0             0             0             5             4
Participant defaulted             0             0             0             0             0             34             18
Un-specified             0             0             0             0             0             7             4
Arm/Group Title Maraviroc QD Maraviroc BID Placebo Total
Hide Arm/Group Description Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning. Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Total of all reporting groups
Overall Number of Baseline Participants 232 235 118 585
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 232 participants 235 participants 118 participants 585 participants
Less than 18 years 0 0 0 0
18 to 24 years 1 0 0 1
25 to 34 years 10 7 5 22
35 to 44 years 97 108 48 253
45 to 54 years 93 90 45 228
55 to 64 years 26 28 19 73
Greater than or equal to 65 years 5 2 1 8
[1]
Measure Description: Out of a total of 601 participants, data for baseline measure (age) was available for 585 participants who were treated.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 232 participants 235 participants 118 participants 585 participants
Female
22
   9.5%
23
   9.8%
12
  10.2%
57
   9.7%
Male
210
  90.5%
212
  90.2%
106
  89.8%
528
  90.3%
[1]
Measure Description: Out of a total of 601 participants, data for baseline measure (gender) was available for 585 participants who were treated.
1.Primary Outcome
Title Log 10-transformed Human Immunodeficiency Virus Ribonucleic Acid (HIV-1 RNA) Levels at Baseline
Hide Description Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and immediately pre-dose.
Time Frame Baseline
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all the randomized participants who had taken at least one dose of the study medication.
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Overall Number of Participants Analyzed 232 235 118
Mean (Standard Deviation)
Unit of Measure: log10 copies/milliliter(log10 copies/mL)
4.854  (0.641) 4.861  (0.614) 4.840  (0.556)
2.Primary Outcome
Title Change From Baseline in Log 10-transformed HIV-1 RNA Levels at Week 24
Hide Description Change from baseline in log 10-transformed plasma viral load (HIV-1 RNA) levels (log10 copies/mL). Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and immediately pre-dose.
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS included all the randomized participants who had taken at least one dose of the study medication. Missing values for viral load at week 24 have been imputed as baseline value for the participants who discontinued and as Last observation carried forward (LOCF) for participants who did not discontinue.
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Overall Number of Participants Analyzed 232 235 118
Least Squares Mean (Standard Error)
Unit of Measure: log10 copies/mL
-1.818  (0.0920) -1.952  (0.0913) -1.030  (0.1287)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments The difference between the treatment least square means (LS means) adjusted for the randomization strata was presented in addition to 2-sided 97.5% confidence interval (CI) as an adjustment for multiplicity using a Bonferroni correction. Negative value favors maraviroc over placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.788
Confidence Interval (2-Sided) 97.5%
-1.141 to -0.435
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1571
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 97.5% CI as an adjustment for multiplicity using a Bonferroni correction. Negative value favors maraviroc over placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.922
Confidence Interval (2-Sided) 97.5%
-1.275 to -0.570
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1568
Estimation Comments [Not Specified]
3.Primary Outcome
Title Change From Baseline in Log 10-transformed HIV-1 RNA Levels at Week 48
Hide Description Change from baseline in log 10-transformed plasma viral load (HIV-1 RNA) levels (log10 copies/mL). Baseline value calculated as average of pre-dose measurements collected at screening, randomization and immediately pre-dose.
Time Frame Baseline and Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS included all the randomized participants who had taken at least one dose of the study medication. Missing values for viral load at week 48 have been imputed as the baseline value for participants who discontinued and as LOCF for participants who did not discontinue.
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Overall Number of Participants Analyzed 232 235 118
Least Squares Mean (Standard Error)
Unit of Measure: log10 copies/mL
-1.656  (0.0949) -1.824  (0.0942) -0.803  (0.1329)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 97.5% CI as an adjustment for multiplicity using a Bonferroni correction. Negative value favors maraviroc over placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.853
Confidence Interval (2-Sided) 97.5%
-1.217 to -0.489
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1621
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 97.5% CI as an adjustment for multiplicity using a Bonferroni correction. Negative value favors maraviroc over placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -1.021
Confidence Interval (2-Sided) 97.5%
-1.385 to -0.658
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1618
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/mL
Hide Description [Not Specified]
Time Frame Week 24 and 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS included all the randomized participants who had taken at least one dose of the study medication. Missing data was imputed as "failure" which was defined as not meeting the criteria of less than 400 copies/mL of HIV-1 RNA levels.
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Overall Number of Participants Analyzed 232 235 118
Measure Type: Number
Unit of Measure: percentage of participants
Week 24 54.7 60.4 31.4
Week 48 50.9 57.5 22.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments Week 24: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (less than [<] 100,000 or greater than or equal to [>=] 100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio greater than (>) 1 favors maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.88
Confidence Interval (2-Sided) 95%
1.78 to 4.67
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments Week 24: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.66
Confidence Interval (2-Sided) 95%
2.26 to 5.95
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments Week 48: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.96
Confidence Interval (2-Sided) 95%
2.36 to 6.64
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments Week 48: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.11
Confidence Interval (2-Sided) 95%
3.04 to 8.59
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/mL or With at Least 0.5 log10 Decrease From Baseline
Hide Description [Not Specified]
Time Frame Week 24 and 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS included all the randomized participants who had taken at least one dose of the study medication. Missing data was imputed as "failure" which was defined as not meeting the criteria of less than 400 copies/mL or with at least 0.5 log10 decrease from baseline of HIV-1 RNA levels.
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Overall Number of Participants Analyzed 232 235 118
Measure Type: Number
Unit of Measure: percentage of participants
Week 24 67.7 69.4 45.8
Week 48 59.9 64.3 35.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments Week 24: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.60
Confidence Interval (2-Sided) 95%
1.63 to 4.13
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments Week 24: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.85
Confidence Interval (2-Sided) 95%
1.79 to 4.54
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments Week 48: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.93
Confidence Interval (2-Sided) 95%
1.83 to 4.67
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments Week 48: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.33
Confidence Interval (2-Sided) 95%
2.08 to 5.32
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/mL or With at Least 1.0 log10 Decrease From Baseline
Hide Description [Not Specified]
Time Frame Week 24 and 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS included all the randomized participants who had taken at least one dose of the study medication. Missing data was imputed as "failure" which was defined as not meeting the criteria of less than 400 copies/mL or with at least 1.0 log10 decrease from baseline of HIV-1 RNA levels.
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Overall Number of Participants Analyzed 232 235 118
Measure Type: Number
Unit of Measure: percentage of participants
Week 24 64.7 67.7 38.1
Week 48 57.8 63.0 31.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments Week 24: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.06
Confidence Interval (2-Sided) 95%
1.92 to 4.88
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments Week 24: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.55
Confidence Interval (2-Sided) 95%
2.22 to 5.68
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments Week 48: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.30
Confidence Interval (2-Sided) 95%
2.05 to 5.31
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments Week 48: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.03
Confidence Interval (2-Sided) 95%
2.50 to 6.51
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Percentage of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL
Hide Description [Not Specified]
Time Frame Week 24 and 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS included all the randomized participants who had taken at least one dose of the study medication. Missing data was imputed as "failure" which was defined as not meeting the criteria of less than 50 copies/mL of HIV-1 RNA levels.
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Overall Number of Participants Analyzed 232 235 118
Measure Type: Number
Unit of Measure: percentage of participants
Week 24 42.2 48.5 24.6
Week 48 41.8 46.8 16.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments Week 24: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.43
Confidence Interval (2-Sided) 95%
1.46 to 4.04
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments Week 24: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.15
Confidence Interval (2-Sided) 95%
1.90 to 5.23
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments Week 48: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.10
Confidence Interval (2-Sided) 95%
2.32 to 7.25
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments Week 48: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.97
Confidence Interval (2-Sided) 95%
2.82 to 8.77
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Cluster of Differentiation 4 (CD4) and Cluster of Differentiation 8 (CD8) Cell Count at Baseline
Hide Description Baseline value calculated as average of pre-dose measurements collected at screening and immediately pre-dose.
Time Frame Baseline
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS included all the randomized participants who had taken at least one dose of the study medication. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Overall Number of Participants Analyzed 231 235 118
Mean (Standard Deviation)
Unit of Measure: cells per microliter (cells/µL)
CD4 187.5  (149.88) 176.5  (143.93) 178.5  (127.09)
CD8 941.1  (556.53) 880.1  (547.19) 880.4  (489.28)
9.Secondary Outcome
Title Change From Baseline in CD4 Cell Count at Week 24 and 48
Hide Description Change from baseline in CD4 cell count measured as cells/µL. Baseline value calculated as the average of pre-dose measurements collected at screening and immediately pre-dose.
Time Frame Baseline, Week 24 and 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS included all the randomized participants who had taken at least one dose of the study medication. 'N' (number of participants analyzed) signifies participants evaluable for this measure. Missing values were imputed using LOCF.
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Overall Number of Participants Analyzed 227 233 116
Least Squares Mean (Standard Error)
Unit of Measure: cells/µL
Week 24 106.63  (7.255) 111.08  (7.148) 52.14  (10.140)
Week 48 112.53  (7.390) 122.44  (7.284) 53.97  (10.341)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments Week 24: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Positive value favors maraviroc over placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 54.49
Confidence Interval (2-Sided) 95%
30.07 to 78.92
Parameter Dispersion
Type: Standard Error of the mean
Value: 12.435
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments Week 24: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Positive value favors maraviroc over placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 58.94
Confidence Interval (2-Sided) 95%
34.63 to 83.26
Parameter Dispersion
Type: Standard Error of the mean
Value: 12.378
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments Week 48: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Positive value favors maraviroc over placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 58.56
Confidence Interval (2-Sided) 95%
33.66 to 83.46
Parameter Dispersion
Type: Standard Error of the mean
Value: 12.677
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments Week 48: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Positive value favors maraviroc over placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 68.47
Confidence Interval (2-Sided) 95%
43.69 to 93.25
Parameter Dispersion
Type: Standard Error of the mean
Value: 12.617
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in CD8 Cell Count at Week 24 and 48
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 and immediately pre-dose.
Time Frame Baseline, Week 24 and 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS included all the randomized participants who had taken at least one dose of the study medication. 'N' (number of participants analyzed) signifies participants evaluable for this measure. Missing values were imputed using LOCF.
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Overall Number of Participants Analyzed 227 233 116
Least Squares Mean (Standard Error)
Unit of Measure: cells/µL
Week 24 283.48  (30.206) 302.33  (29.745) -0.74  (42.198)
Week 48 198.00  (28.962) 220.40  (28.532) -15.34  (40.503)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments Week 24: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Positive value favors maraviroc over placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 284.21
Confidence Interval (2-Sided) 95%
182.51 to 385.92
Parameter Dispersion
Type: Standard Error of the mean
Value: 51.779
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments Week 24: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Positive value favors maraviroc over placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 303.07
Confidence Interval (2-Sided) 95%
201.90 to 404.23
Parameter Dispersion
Type: Standard Error of the mean
Value: 51.507
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments Week 48: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Positive value favors maraviroc over placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 213.34
Confidence Interval (2-Sided) 95%
115.77 to 310.92
Parameter Dispersion
Type: Standard Error of the mean
Value: 49.679
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments Week 48: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Positive value favors maraviroc over placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 235.74
Confidence Interval (2-Sided) 95%
138.68 to 332.80
Parameter Dispersion
Type: Standard Error of the mean
Value: 49.416
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Time to Virological Failure
Hide Description Time to virologic failure based on observed HIV-1 RNA levels and failure events (death;permanent discontinuation of drug;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 events or last available visit;at time of earliest event if level <400 copies/mL(2 consecutive visits);failure if level >=400 copies/mL(2 consecutive visits) or 1 visit >=400 copies/mL followed by permanent discontinuation of drug or LTFU.
Time Frame Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS included all the randomized participants who had taken at least one dose of the study medication.
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Overall Number of Participants Analyzed 232 235 118
Median (95% Confidence Interval)
Unit of Measure: days
344.00
(195.00 to 372.00)
NA [1] 
(NA to NA)
0.00 [2] 
(NA to NA)
[1]
Data was not estimable because less than 50% of participants experienced virological failure.
[2]
Data was not estimable because the empirical distribution of the data rendered the algorithmic formula non-calculable.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments P-value was calculated using Log rank test controlling for the effect of the randomization strata. Hazard ratio calculated by fitting a Cox proportional hazards model including treatment group and randomization strata. Hazard ratio <1 favors maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.45
Confidence Interval (2-Sided) 95%
0.34 to 0.60
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments P-value was calculated using Log rank test controlling for the effect of the randomization strata. Hazard ratio calculated by fitting a Cox proportional hazards model including treatment group and randomization strata. Hazard ratio <1 favors maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.38
Confidence Interval (2-Sided) 95%
0.28 to 0.50
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Time-Averaged Difference (TAD) From Baseline in log10 Transformed HIV-1 RNA Levels
Hide Description TAD from baseline was calculated as area under the curve of HIV-1 RNA load (log10 copies/mL) divided by time period minus baseline HIV-1 RNA load (log10 copies/mL). Baseline value calculated as the average of pre-dose measurements collected at screening, randomization, and immediately pre-dose.
Time Frame Baseline to Week 24 and Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS included all the randomized participants who had taken at least one dose of the study medication. Missing data imputed as 0 for participants who discontinued and through last available observation for participants who did not discontinue.
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Overall Number of Participants Analyzed 232 235 118
Least Squares Mean (Standard Error)
Unit of Measure: log10 copies/mL
Week 24 -1.636  (0.0789) -1.741  (0.0783) -0.939  (0.1103)
Week 48 -1.556  (0.0876) -1.720  (0.0870) -0.788  (0.1227)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments Week 24: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Negative value favors maraviroc over placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.697
Confidence Interval (2-Sided) 95%
-0.961 to -0.432
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1347
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments Week 24: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Negative value favors maraviroc over placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.802
Confidence Interval (2-Sided) 95%
-1.065 to -0.538
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1344
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
Comments Week 48: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Negative value favors maraviroc over placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.767
Confidence Interval (2-Sided) 95%
-1.061 to -0.474
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1497
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
Comments Week 48: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Negative value favors maraviroc over placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.931
Confidence Interval (2-Sided) 95%
-1.225 to -0.638
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1494
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Number of Participants With Genotypic Susceptibility Scores (GSS) and Phenotypic Susceptibility Score (PSS) at Screening
Hide Description Number of participants with GSS and PSS were used as surrogates for assessing genotype and phenotype. Genotypic and phenotypic resistance to protease inhibitors(PIs), nucleoside reverse transcriptase inhibitors(NRTIs), non-nucleoside reverse transcriptase inhibitors(NNRTIs) were evaluated at screening (not at baseline), by Monogram Biosciences PhenoSense genotyping (GT) assay. Score was determined for each drug in OBT, giving 1:drug ‘sensitive'/'susceptible' and 0:'resistant'. GSS and PSS score range:0 to >3. Genotypic enfuvirtide value was used for PSS, no phenotypic enfuvirtide was recorded.
Time Frame Screening
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS included all the randomized participants who had taken at least one dose of the study medication.
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Overall Number of Participants Analyzed 232 235 118
Measure Type: Number
Unit of Measure: participants
GSS: 0 52 59 31
GSS: 1 82 80 29
GSS: 2 38 48 21
GSS: greater than or equal to 3 57 47 34
GSS: missing 3 1 3
PSS: 0 25 24 17
PSS: 1 70 73 18
PSS: 2 51 69 35
PSS: greater than or equal to 3 83 66 45
PSS: missing 3 3 3
14.Secondary Outcome
Title Number of Participants With Change in GSS and PSS From Screening at the Time of Treatment Failure Through Week 24
Hide Description Number of participants with GSS and PSS were used as surrogates for assessing genotype and phenotype. Genotypic and phenotypic resistance to PIs, NRTIs and NNRTIs were evaluated at screening and time of treatment failure analyzed through week 24 visit, by Monogram Biosciences PhenoSense GT assay. Score was determined for each drug in OBT, giving 1: drug ‘sensitive'/'susceptible' and 0: 'resistant'. GSS and PSS score range:0 to >3. Genotypic enfuvirtide value was used for PSS, no phenotypic enfuvirtide was recorded.
Time Frame Screening and time of failure through week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS; ‘N’ (number of participants analyzed) is signifying those participants who experienced treatment failure defined as discontinuation due to insufficient response. 'n' is number of participants who were evaluable for the given change in GSS and PSS score for each arm group respectively.
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Overall Number of Participants Analyzed 42 46 53
Measure Type: Number
Unit of Measure: participants
Change in GSS by less than -3 (n= 35 ,40, 47) 0 0 1
Change in GSS by -3 (n= 35 ,40, 47) 0 0 0
Change in GSS by -2 (n= 35 ,40, 47) 3 0 1
Change in GSS by -1 (n= 35 ,40, 47) 9 13 11
Change in GSS by 0 (n= 35 ,40, 47) 23 26 32
Change in GSS by 1 (n= 35 ,40, 47) 0 1 1
Change in GSS by 2 (n= 35 ,40, 47) 0 0 0
Change in GSS by 3 (n= 35 ,40, 47) 0 0 1
Change in GSS by greater than 3 (n= 35 ,40, 47) 0 0 0
Change in PSS by less than -3 (n= 35 ,40, 45) 0 0 1
Change in PSS by -3 (n= 35 ,40, 45) 4 1 1
Change in PSS by -2 (n= 35 ,40, 45) 4 1 4
Change in PSS by -1 (n= 35 ,40, 45) 10 18 12
Change in PSS by 0 (n= 35 ,40, 45) 15 17 25
Change in PSS by 1 (n= 35 ,40, 45) 2 3 2
Change in PSS by 2 (n= 35 ,40, 45) 0 0 0
Change in PSS by 3 (n= 35 ,40, 45) 0 0 0
Change in PSS by greater than 3 (n= 35 ,40, 45) 0 0 0
15.Secondary Outcome
Title Number of Participants With Change in GSS and PSS From Screening at the Time of Treatment Failure at Week 48
Hide Description Number of participants with GSS and PSS were used as surrogates for assessing genotype and phenotype. Genotypic and phenotypic resistance to PIs, NRTIs and NNRTIs were evaluated at screening and time of treatment failure analyzed through week 48 visit, by Monogram Biosciences PhenoSense GT assay. Score was determined for each drug in OBT, giving 1: drug ‘sensitive'/'susceptible' and 0: 'resistant'. GSS and PSS score range:0 to >3. Genotypic enfuvirtide value was used for PSS, no phenotypic enfuvirtide was recorded.
Time Frame Screening and time of failure through week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS; ‘N’ (number of participants analyzed) is signifying those participants who experienced treatment failure defined as discontinuation due to discontinuation due to insufficient response. 'n' is number of participants who were evaluable for the given change in GSS and PSS score for each arm group respectively.
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Overall Number of Participants Analyzed 51 58 62
Measure Type: Number
Unit of Measure: participants
Change in GSS by less than -3 (n= 44 ,52, 55) 0 0 1
Change in GSS by -3 (n= 44 ,52, 55) 0 0 1
Change in GSS by -2 (n= 44 ,52, 55) 5 1 2
Change in GSS by -1 (n= 44 ,52, 55) 12 17 15
Change in GSS by 0 (n= 44 ,52, 55) 26 31 33
Change in GSS by 1 (n= 44 ,52, 55) 1 2 1
Change in GSS by 2 (n= 44 ,52, 55) 0 1 1
Change in GSS by 3 (n= 44 ,52, 55) 0 0 1
Change in GSS by greater than 3 (n= 44 ,52, 55) 0 0 0
Change in PSS by less than -3 (n= 44 , 52, 53) 0 1 1
Change in PSS by -3 (n= 44 , 52, 53) 4 1 3
Change in PSS by -2 (n= 44 , 52, 53) 6 3 6
Change in PSS by -1 (n= 44 , 52, 53) 13 21 12
Change in PSS by 0 (n= 44 , 52, 53) 17 23 26
Change in PSS by 1 (n= 44 , 52, 53) 3 3 4
Change in PSS by 2 (n= 44 , 52, 53) 0 0 1
Change in PSS by 3 (n= 44 , 52, 53) 1 0 0
Change in PSS by greater than 3 (n= 44 , 52, 53) 0 0 0
16.Secondary Outcome
Title Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 24
Hide Description Number of participants per tropism status (C-X-C chemokine receptor 5 {CCR5} [R5], C-X-C chemokine receptor type 4 {CXCR4} [X4], Dual/mixed [DM], or Non-reportable/Non-phenotypable [NR/NP]) at baseline and time of treatment failure analyzed through week 24 visit. Treatment failure defined as discontinuation due to insufficient clinical response. HIV-1 RNA viral load <500 copies/mL categorized as below lower limit of quantification (BLQ). The assessment for time of treatment failure was defined as the last on treatment assessment.
Time Frame Baseline and time of failure through week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS; ‘N’ (number of participants analyzed) is signifying those participants who experienced treatment failure, defined as discontinuation due to insufficient response and had tropism assessment at baseline.
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Description Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Overall Number of Participants Analyzed 42 46 53
Measure Type: Number
Unit of Measure: participants
Baseline: R5; Treatment failure: R5 10 10 44
Baseline: R5; Treatment failure: X4 6 5 0
Baseline: R5; Treatment failure: DM 18 19 1
Baseline: R5; Treatment failure: NR/NP 1 3 3
Baseline: DM; Treatment failure: R5 0 0 1
Baseline: DM; Treatment failure: X4 1 4 1
Baseline: DM; Treatment failure: DM 3 4 1
Baseline: DM; Treatment failure: NR/NP 1 1 0
17.Secondary Outcome
Title Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 48
Hide Description Number of participants per tropism status (R5, X4, DM, or NR/NP) at baseline and time of treatment failure analyzed through week 48 visit. Treatment failure defined as insufficient clinical response. HIV-1 RNA viral load <500 copies/mL categorized as BLQ. The assessment for time of treatment failure was defined as the last on treatment assessment.
Time Frame Baseline and time of failure through week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS; ‘N’ (number of participants analyzed) is signifying those participants who experienced treatment failure, defined as discontinuation due to insufficient response and had tropism assessment at baseline.
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Overall Number of Participants Analyzed 51 58 62
Measure Type: Number
Unit of Measure: participants
Baseline: R5, Treatment failure: R5 16 15 49
Baseline: R5, Treatment failure: X4 6 7 0
Baseline: R5, Treatment failure: DM 19 22 3
Baseline: R5, Treatment failure: NR/NP 1 3 3
Baseline: DM, Treatment failure: R5 0 0 2
Baseline: DM, Treatment failure: X4 2 4 1
Baseline: DM, Treatment failure: DM 4 5 1
Baseline: DM, Treatment failure: NR/NP 2 1 0
18.Secondary Outcome
Title Change From Baseline in Viral Load at Week 24 and Week 48 by Overall Susceptibility Score (OSS) at Screening
Hide Description Association between baseline resistance and virological response was assessed as change in viral load by OSS at screening. OSS categorized as 0, 1, 2, >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= resistant, 1= sensitive or susceptible) for each antiretroviral agent in OBT. Higher scores indicate greater susceptibility. Baseline value is the average of the values from screening, randomization and immediately pre-dose.
Time Frame Baseline, Week 24 and Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS; 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure. 'n' is number of participants with given OSS score at screening for each treatment arm at particular time-point. LOCF was used to impute missing values.
Arm/Group Title Maraviroc QD Maraviroc BID Placebo
Hide Arm/Group Description:
Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Overall Number of Participants Analyzed 228 234 116
Mean (Standard Deviation)
Unit of Measure: log10copies/mL
Week 24; Screening OSS 0 (n= 29, 27, 19) -0.945  (0.905) -1.524  (1.331) -0.083  (0.472)
Week 24; Screening OSS 1 (n= 76, 86, 21) -1.911  (1.229) -1.895  (1.395) -0.350  (0.784)
Week 24; Screening OSS 2 (n= 51, 65, 38) -2.093  (1.3402) -2.220  (1.0900) -1.251  (1.0800)
Week 24; Screening OSS >=3 (n= 68, 53, 35) -2.536  (1.1599) -2.672  (1.1836) -2.471  (0.9200)
Week 24; Screening OSS= Missing (n= 4, 3, 3) -2.070  (1.3832) -3.075  (0.5705) -0.530  (0.1726)
Week 48; Screening OSS 0 (n= 29, 27, 19) -0.876  (0.8448) -1.419  (1.3042) -0.088  (0.4541)
Week 48; Screening OSS 1 (n= 77, 86, 20) -1.843  (1.2452) -1.868  (1.4078) -0.262  (0.7048)
Week 48; Screening OSS 2 (n= 51, 64, 38) -2.146  (1.4208) -2.182  (1.1096) -1.147  (0.9681)
Week 48; Screening OSS >=3 (n= 67, 54, 36) -2.427  (1.3136) -2.634  (1.1628) -2.205  (1.0870)
Week 48; Screening OSS= Missing (n= 4, 3, 3) -2.106  (1.4461) -2.698  (1.2056) -0.370  (0.1471)
Time Frame [Not Specified]
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
 
Arm/Group Title Maraviroc QD, Double Blind Maraviroc BID, Double Blind Placebo, Double Blind Maraviroc BID, Open Label In Study-off Drug (ISOD), Open Label Maraviroc BID, Observation Phase In Study-off Drug (ISOD), Observation Phase
Hide Arm/Group Description Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning. Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Participants from maraviroc QD, maraviroc BID and Placebo (double blind phase) who received maraviroc 150 or 300 mg BID in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) during open label phase. Participants from maraviroc QD, maraviroc BID and Placebo (double blind phase) who received no study treatment along with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) in during open label phase. Participants continuing from open label phase, who received maraviroc 150 or 300 mg BID in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) during observational phase. Participants continuing from open label phase, who received no study treatment along with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) during observational phase.
All-Cause Mortality
Maraviroc QD, Double Blind Maraviroc BID, Double Blind Placebo, Double Blind Maraviroc BID, Open Label In Study-off Drug (ISOD), Open Label Maraviroc BID, Observation Phase In Study-off Drug (ISOD), Observation Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Maraviroc QD, Double Blind Maraviroc BID, Double Blind Placebo, Double Blind Maraviroc BID, Open Label In Study-off Drug (ISOD), Open Label Maraviroc BID, Observation Phase In Study-off Drug (ISOD), Observation Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   42/232 (18.10%)   53/235 (22.55%)   20/118 (16.95%)   33/327 (10.09%)   0/62 (0.00%)   0/250 (0.00%)   0/81 (0.00%) 
Blood and lymphatic system disorders               
Anaemia * 1  2/232 (0.86%)  1/235 (0.43%)  1/118 (0.85%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Febrile neutropenia * 1  0/232 (0.00%)  1/235 (0.43%)  1/118 (0.85%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Lymphadenopathy * 1  0/232 (0.00%)  0/235 (0.00%)  1/118 (0.85%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Splenomegaly * 1  0/232 (0.00%)  1/235 (0.43%)  1/118 (0.85%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Thrombotic thrombocytopenic purpura * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Neutropenia * 1  0/232 (0.00%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Thrombocytopenia * 1  0/232 (0.00%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Cardiac disorders               
Acute myocardial infarction * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Angina pectoris * 1  1/232 (0.43%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Angina unstable * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Myocardial ischaemia * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Tachycardia * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Cardiac arrest * 1  0/232 (0.00%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Cardiac failure congestive * 1  0/232 (0.00%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Coronary artery disease * 1  0/232 (0.00%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Myocardial infarction * 1  0/232 (0.00%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Eye disorders               
Blindness unilateral * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Visual impairment * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Gastrointestinal disorders               
Abdominal discomfort * 1  0/232 (0.00%)  0/235 (0.00%)  1/118 (0.85%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Abdominal pain * 1  2/232 (0.86%)  1/235 (0.43%)  2/118 (1.69%)  2/327 (0.61%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Ascites * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Colitis * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Diarrhoea * 1  2/232 (0.86%)  1/235 (0.43%)  0/118 (0.00%)  3/327 (0.92%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Diarrhoea haemorrhagic * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Diverticulum intestinal haemorrhagic * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Dysphagia * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Haematochezia * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Nausea * 1  2/232 (0.86%)  1/235 (0.43%)  1/118 (0.85%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Odynophagia * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Oesophageal stenosis * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Oesophagitis * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Pancreatitis * 1  2/232 (0.86%)  0/235 (0.00%)  1/118 (0.85%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Proctalgia * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Small intestinal obstruction * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Varices oesophageal * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Vomiting * 1  3/232 (1.29%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Proctitis * 1  0/232 (0.00%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Rectal haemorrhage * 1  0/232 (0.00%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Abdominal pain upper * 1  1/232 (0.43%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
General disorders               
Asthenia * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Chest pain * 1  3/232 (1.29%)  1/235 (0.43%)  2/118 (1.69%)  2/327 (0.61%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Malaise * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Pyrexia * 1  2/232 (0.86%)  5/235 (2.13%)  1/118 (0.85%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Hepatobiliary disorders               
Cholecystitis * 1  0/232 (0.00%)  2/235 (0.85%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Cholelithiasis * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Hepatic cirrhosis * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Hepatic failure * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Hepatomegaly * 1  0/232 (0.00%)  0/235 (0.00%)  1/118 (0.85%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Hepatotoxicity * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Hyperbilirubinaemia * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Portal vein thrombosis * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Immune system disorders               
Antiphospholipid syndrome * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Drug hypersensitivity * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Infections and infestations               
Abscess * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Abscess limb * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Appendicitis * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Arthritis bacterial * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Arthritis gonococcal * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Bronchitis * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Cavernous sinus thrombosis * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Cellulitis * 1  1/232 (0.43%)  2/235 (0.85%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Clostridium difficile colitis * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Cystitis * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Cytomegalovirus chorioretinitis * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Diverticulitis * 1  0/232 (0.00%)  1/235 (0.43%)  1/118 (0.85%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Fungal infection * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Gangrene * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Gastric infection * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Gastroenteritis * 1  2/232 (0.86%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Gastroenteritis bacterial * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Gastroenteritis viral * 1  1/232 (0.43%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Genital herpes * 1  0/232 (0.00%)  0/235 (0.00%)  1/118 (0.85%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Groin abscess * 1  0/232 (0.00%)  0/235 (0.00%)  1/118 (0.85%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
HIV wasting syndrome * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Herpes simplex * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Infective myositis * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Meningitis viral * 1  0/232 (0.00%)  2/235 (0.85%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Oesophageal candidiasis * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Pharyngitis * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/0  0/81 (0.00%) 
Pneumonia * 1  7/232 (3.02%)  2/235 (0.85%)  4/118 (3.39%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Progressive multifocal leukoencephalopathy * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Pyelonephritis * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Rectal abscess * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Sepsis * 1  0/232 (0.00%)  0/235 (0.00%)  1/118 (0.85%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Sinusitis * 1  1/232 (0.43%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Staphylococcal infection * 1  0/232 (0.00%)  0/235 (0.00%)  1/118 (0.85%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Upper respiratory tract infection * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Urethral abscess * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Abdominal wall abscess * 1  0/232 (0.00%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
HIV infection * 1  0/232 (0.00%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Lung infection * 1  0/232 (0.00%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Mycobacterium avium complex infection * 1  0/232 (0.00%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Osteomyelitis * 1  0/232 (0.00%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Pneumonia bacterial * 1  0/232 (0.00%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Urinary tract infection * 1  0/232 (0.00%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Injury, poisoning and procedural complications               
Drug toxicity * 1  0/232 (0.00%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Fall * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Hip fracture * 1  0/232 (0.00%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Heat exhaustion * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Intentional overdose * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Investigations               
Alanine aminotransferase increased * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Aspartate aminotransferase increased * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Blood amylase increased * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Gamma-glutamyltransferase increased * 1  0/232 (0.00%)  0/235 (0.00%)  1/118 (0.85%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Lipase increased * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Transaminases increased * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Blood creatine phosphokinase increased * 1  0/232 (0.00%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Nuclear magnetic resonance imaging brain * 1  0/232 (0.00%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Weight decreased * 1  0/232 (0.00%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Metabolism and nutrition disorders               
Dehydration * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Hyperglycaemia * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Lactic acidosis * 1  0/232 (0.00%)  0/235 (0.00%)  1/118 (0.85%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Musculoskeletal and connective tissue disorders               
Arthralgia * 1  0/232 (0.00%)  2/235 (0.85%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Intervertebral disc degeneration * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Intervertebral disc protrusion * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Joint range of motion decreased * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Joint swelling * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Joint warmth * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Musculoskeletal pain * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Osteonecrosis * 1  1/232 (0.43%)  2/235 (0.85%)  0/118 (0.00%)  2/327 (0.61%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Pain in extremity * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Rhabdomyolysis * 1  0/232 (0.00%)  2/235 (0.85%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Spinal disorder * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Anal cancer * 1  2/232 (0.86%)  2/235 (0.85%)  1/118 (0.85%)  2/327 (0.61%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
B-cell lymphoma * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  2/327 (0.61%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Diffuse large B-cell lymphoma * 1  0/232 (0.00%)  0/235 (0.00%)  1/118 (0.85%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Hodgkin’s disease * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Lymphoma * 1  1/232 (0.43%)  0/235 (0.00%)  1/118 (0.85%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Oesophageal carcinoma * 1  1/232 (0.43%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Rectal cancer * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Squamous cell carcinoma * 1  0/232 (0.00%)  1/235 (0.43%)  1/118 (0.85%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Sweat gland tumour * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
T-cell lymphoma * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Leukaemia * 1  0/232 (0.00%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Nervous system disorders               
Cerebrovascular accident * 1  2/232 (0.86%)  2/235 (0.85%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Convulsion * 1  1/232 (0.43%)  1/235 (0.43%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Encephalopathy * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Headache * 1  1/232 (0.43%)  0/235 (0.00%)  1/118 (0.85%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Hypoaesthesia * 1  0/232 (0.00%)  0/235 (0.00%)  1/118 (0.85%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Memory impairment * 1  0/232 (0.00%)  0/235 (0.00%)  1/118 (0.85%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Paraesthesia * 1  0/232 (0.00%)  0/235 (0.00%)  1/118 (0.85%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Sedation * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Speech disorder * 1  0/232 (0.00%)  0/235 (0.00%)  1/118 (0.85%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Syncope * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Transient ischaemic attack * 1  0/232 (0.00%)  0/235 (0.00%)  2/118 (1.69%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Cerebral infarction * 1  0/232 (0.00%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Dizziness * 1  0/232 (0.00%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Pneumocephalus * 1  0/232 (0.00%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Pregnancy, puerperium and perinatal conditions               
Pregnancy * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Psychiatric disorders               
Anxiety * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Confusional state * 1  0/232 (0.00%)  0/235 (0.00%)  1/118 (0.85%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Schizophrenia * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Suicide attempt * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Psychotic disorder * 1  0/232 (0.00%)  0/235 (0.00%)  0/118 (0.00%)  2/327 (0.61%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Renal and urinary disorders               
Nephrolithiasis * 1  1/232 (0.43%)  2/235 (0.85%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Renal failure * 1  1/232 (0.43%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Renal failure acute * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Bronchial hyperreactivity * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Cough * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Dyspnoea * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Hypoxia * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Lung infiltration * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Pneumonia aspiration * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Pneumonitis * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Pneumothorax * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Pulmonary embolism * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Skin and subcutaneous tissue disorders               
Erythema * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Rash * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Rash generalised * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Surgical and medical procedures               
Hip surgery * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Plasmapheresis * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Stent placement * 1  0/232 (0.00%)  0/235 (0.00%)  1/118 (0.85%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Toe operation * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Vascular disorders               
Deep vein thrombosis * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Hypertension * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Hypotension * 1  1/232 (0.43%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Peripheral embolism * 1  0/232 (0.00%)  1/235 (0.43%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Infarction * 1  0/232 (0.00%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Thrombophlebitis * 1  0/232 (0.00%)  0/235 (0.00%)  0/118 (0.00%)  1/327 (0.31%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 13.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Maraviroc QD, Double Blind Maraviroc BID, Double Blind Placebo, Double Blind Maraviroc BID, Open Label In Study-off Drug (ISOD), Open Label Maraviroc BID, Observation Phase In Study-off Drug (ISOD), Observation Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   170/232 (73.28%)   192/235 (81.70%)   89/118 (75.42%)   19/327 (5.81%)   0/62 (0.00%)   0/250 (0.00%)   0/81 (0.00%) 
Gastrointestinal disorders               
Abdominal distension * 1  13/232 (5.60%)  9/235 (3.83%)  4/118 (3.39%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Abdominal pain * 1  12/232 (5.17%)  13/235 (5.53%)  1/118 (0.85%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Constipation * 1  12/232 (5.17%)  16/235 (6.81%)  0/118 (0.00%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Diarrhoea * 1  58/232 (25.00%)  53/235 (22.55%)  30/118 (25.42%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Nausea * 1  45/232 (19.40%)  48/235 (20.43%)  23/118 (19.49%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Vomiting * 1  20/232 (8.62%)  15/235 (6.38%)  12/118 (10.17%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
General disorders               
Fatigue * 1  36/232 (15.52%)  46/235 (19.57%)  22/118 (18.64%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Injection site reaction * 1  20/232 (8.62%)  24/235 (10.21%)  14/118 (11.86%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Malaise * 1  3/232 (1.29%)  1/235 (0.43%)  6/118 (5.08%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Oedema peripheral * 1  13/232 (5.60%)  9/235 (3.83%)  3/118 (2.54%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Pyrexia * 1  19/232 (8.19%)  32/235 (13.62%)  13/118 (11.02%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Infections and infestations               
Bronchitis * 1  20/232 (8.62%)  20/235 (8.51%)  9/118 (7.63%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Folliculitis * 1  5/232 (2.16%)  12/235 (5.11%)  3/118 (2.54%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Nasopharyngitis * 1  14/232 (6.03%)  19/235 (8.09%)  9/118 (7.63%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Sinusitis * 1  15/232 (6.47%)  24/235 (10.21%)  5/118 (4.24%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Upper respiratory tract infection * 1  36/232 (15.52%)  35/235 (14.89%)  10/118 (8.47%)  19/327 (5.81%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Investigations               
Weight decreased * 1  14/232 (6.03%)  8/235 (3.40%)  2/118 (1.69%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Metabolism and nutrition disorders               
Decreased appetite * 1  19/232 (8.19%)  17/235 (7.23%)  4/118 (3.39%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Musculoskeletal and connective tissue disorders               
Arthralgia * 1  19/232 (8.19%)  20/235 (8.51%)  3/118 (2.54%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Back pain * 1  11/232 (4.74%)  20/235 (8.51%)  8/118 (6.78%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Muscle spasms * 1  14/232 (6.03%)  6/235 (2.55%)  5/118 (4.24%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Pain in extremity * 1  12/232 (5.17%)  11/235 (4.68%)  5/118 (4.24%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Nervous system disorders               
Dizziness * 1  27/232 (11.64%)  25/235 (10.64%)  9/118 (7.63%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Headache * 1  34/232 (14.66%)  35/235 (14.89%)  19/118 (16.10%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Hypoaesthesia * 1  12/232 (5.17%)  9/235 (3.83%)  1/118 (0.85%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Psychiatric disorders               
Depression * 1  15/232 (6.47%)  14/235 (5.96%)  4/118 (3.39%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Insomnia * 1  22/232 (9.48%)  25/235 (10.64%)  7/118 (5.93%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Cough * 1  31/232 (13.36%)  37/235 (15.74%)  8/118 (6.78%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Nasal congestion * 1  10/232 (4.31%)  15/235 (6.38%)  4/118 (3.39%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Oropharyngeal pain * 1  14/232 (6.03%)  16/235 (6.81%)  4/118 (3.39%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Sinus congestion * 1  11/232 (4.74%)  12/235 (5.11%)  2/118 (1.69%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Skin and subcutaneous tissue disorders               
Night sweats * 1  10/232 (4.31%)  16/235 (6.81%)  3/118 (2.54%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Rash * 1  19/232 (8.19%)  24/235 (10.21%)  6/118 (5.08%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
Vascular disorders               
Hypertension * 1  6/232 (2.59%)  12/235 (5.11%)  1/118 (0.85%)  0/327 (0.00%)  0/62 (0.00%)  0/250 (0.00%)  0/81 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 13.0
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 less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 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
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT00098306     History of Changes
Other Study ID Numbers: A4001027
First Submitted: December 6, 2004
First Posted: December 7, 2004
Results First Submitted: April 2, 2012
Results First Posted: April 27, 2012
Last Update Posted: April 27, 2012