| Primary | Change From Baseline in Human Immunodeficiency Virus (HIV-1) Viral Load (Ribonucleic Acid [RNA]) | Change from baseline in log 10-transformed plasma viral load (HIV-1 RNA) levels (log 10 copies per milliliter [log10 copies/mL]). Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and baseline visits. | Full Analysis Set (FAS)-as treated: all randomized subjects classified as dual-tropic by phenotype assay; received at least 1 dose of study treatment. Missing values: discontinuations (DC) imputed as baseline value (change from baseline=0); missing data imputed as Last Observation Carried Forward (LOCF). | Posted | | Mean | Standard Error | log10 copies/mL | | Baseline to Week 24 and Week 48 | | | | ID | Title | Description |
|---|
| OG000 | Maraviroc QD | Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening. | | OG001 | Maraviroc BID | Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening. | | OG002 | Placebo | Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening. |
| | | Title | Denominators | Categories |
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| Week 24 | | | Title | Measurements |
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| - OG000-0.890± 0.1706
- OG001-1.194± 0.2060
- OG002-0.953± 0.1795
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| | Week 48 |
| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
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| Maraviroc (MVC) QD versus placebo (PBO) treatment (TX) difference at Week 24. If upper bound of 97.5% confidence interval is <0, it is concluded that dose is superior to PBO. If upper bound is <0.25, it is concluded that MVC is non-inferior to PBO. Assumption: 79% of subjects are dual-tropic; total N=192 needed to be randomized to get N=150 dual-tropic. Standard deviation=0.8 with 2-sided p-value=0.025: 80% power for TX difference of 0.5 for change from baseline in log10-transformed viral load. | ANCOVA | TX difference adjusted for randomization strata. Bonferroni adjustment for multiple comparisons by use of 2-sided 97.5% CI to maintain alpha=0.05. | | | Least squares mean | 0.055 | Standard Error of the Mean | 0.2575 | 2-Sided | 97.5 | -0.528 | 0.638 | | | |
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| Secondary | Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL | | FAS - as treated dual-tropic subjects. Missing values counted as failures/non-responders (counted as not achieving the stated criterion). | Posted | | Number | | participants | | Week 24, Week 48 | | | | ID | Title | Description |
|---|
| OG000 | Maraviroc QD | Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening. | | OG001 | Maraviroc BID | Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening. | | OG002 | Placebo | Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening. |
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| Secondary | Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 0.5 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels | Number of subjects with HIV-1 RNA levels < 400 copies/mL or at least 0.5 log 10-transformed decrease from baseline in HIV-1 RNA levels. Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and baseline visits. | FAS-as treated dual-tropic subjects. Missing values counted as failures/non-responders (counted as not achieving the stated criterion). | Posted | | Number | | participants | | Baseline, Week 24, Week 48 | | | | ID | Title | Description |
|---|
| OG000 | Maraviroc QD | Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening. | | OG001 | Maraviroc BID | Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening. | | OG002 | Placebo | Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening. |
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| Secondary | Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 1.0 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels | Number of subjects with HIV-1 RNA levels < 400 copies/mL or at least 1.0 log 10-transformed decrease from baseline in HIV-1 RNA levels. Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and baseline visits. | FAS-as treated dual-tropic subjects. Missing values counted as failures/non-responders (counted as not achieving the stated criterion). | Posted | | Number | | participants | | Baseline, Week 24, Week 48 | | | | ID | Title | Description |
|---|
| OG000 | Maraviroc QD | Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening. | | OG001 | Maraviroc BID | Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening. | | OG002 | Placebo | Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening. |
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| Secondary | Number of Subjects With HIV-1 RNA Levels < 50 Copies/mL | | FAS - as treated dual-tropic subjects. Missing values counted as failures/non-responders (counted as not achieving the stated criterion). | Posted | | Number | | participants | | Baseline, Week 24, Week 48 | | | | ID | Title | Description |
|---|
| OG000 | Maraviroc QD | Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening. | | OG001 | Maraviroc BID | Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening. | | OG002 | Placebo | Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening. |
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| Secondary | Change From Baseline in CD4 Cell Count | Change from baseline in CD4 cell count (measured as cells per microliter [cells/µL]). Baseline value calculated as the average of pre-dose measurements collected at screening, randomization, and baseline visits. | FAS - as treated dual-tropic subjects. Placebo N: 4 subjects did not have on-treatment information. Missing data imputed using LOCF. | Posted | | Mean | Standard Error | cells/µL | | Baseline to Week 24 and Week 48 | | | | ID | Title | Description |
|---|
| OG000 | Maraviroc QD | Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening. | | OG001 | Maraviroc BID | Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening. | | OG002 | Placebo | Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening. |
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| Secondary | Change From Baseline in CD8 Cell Count | Change from baseline in CD8 cell count (measured as cells/µL). Baseline value calculated as the average of pre-dose measurements collected at screening, randomization, and baseline visits. | FAS - as treated dual-tropic subjects. Placebo N: 4 subjects did not have on-treatment information. Missing data imputed using LOCF. | Posted | | Mean | Standard Error | cells/µL | | Baseline to Week 24 and Week 48 | | | | ID | Title | Description |
|---|
| OG000 | Maraviroc QD | Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening. | | OG001 | Maraviroc BID | Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening. | | OG002 | Placebo | Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening. |
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| Secondary | Time (50% Quartile Point Estimate) to Virologic Failure | Time to virologic failure based on observed HIV-1 RNA levels and failure events (death; permanent discontinuation of test drug [perm DC]; lost to follow-up [LTFU]; new anti-retroviral drug added (except background drug change to drug of same class); or on open label for early non-response or rebound). Failure: at Time 0 if level not <400 copies/mL (2 consecutive visits) before event(s) or last available visit; at time of earliest event if level <400 copies/mL (on 2 consecutive visits); failure if level ≥400 copies/mL (2 consecutive visits) or 1 visit ≥400 copies/mL followed by perm DC or LTFU. | FAS - as treated dual-tropic subjects; (n)=number of subjects with virologic failure at observation for maraviroc QD, maraviroc BID, and placebo, respectively; Week 48 result values (0.00)=virologic failure at Day 0. | Posted | | Median | 95% Confidence Interval | days | | Day 1 through Week 24 and through Week 48 | | | | ID | Title | Description |
|---|
| OG000 | Maraviroc QD | Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening. | | OG001 | Maraviroc BID | Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening. |
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| Secondary | Change From Baseline in Time Averaged Difference (TAD) in log10 HIV-1 RNA | Change from baseline of TAD in log10 HIV-1 RNA viral load calculated as [AUC of HIV-1 RNA viral load (log10 copies/mL) / time period] - Baseline HIV-1 RNA viral load (log10 copies/mL). Baseline value calculated as the average of pre-dose measurements collected at screening, randomization, and baseline visits. | FAS - as treated dual-tropic subjects. Discontinuations prior to time point of analysis imputed as 0. | Posted | | Mean | Standard Error | log10 copies/mL | | Baseline to Week 24 and Week 48 | | | | ID | Title | Description |
|---|
| OG000 | Maraviroc QD | Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening. | | OG001 | Maraviroc BID | Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening. | | OG002 | Placebo | Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening. |
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| Secondary | Number of Subjects Per Genotype and Phenotype at Baseline and at Time of Failure | Number of subjects per genotype and phenotype (tests for presence of non CCR5-tropic HIV-1 and for resistance to reverse transcriptase, protease, and fusion inhibitors) at baseline and at time of failure through Week 48 visit. Sensitivity to drug categorized as 0-1, 2-4, >4; scores defined as 0=resistance, 1=sensitive or susceptible with higher number indicating greater sensitivity or susceptibility. | FAS-as treated dual-tropic subjects. Genotype and phenotype at screening and at time of failure were not summarized as planned. | Posted | | Number | | participants | | Baseline through Week 48 | | | | ID | Title | Description |
|---|
| OG000 | Maraviroc QD | Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening. | | OG001 | Maraviroc BID | Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening. | | OG002 | Placebo | Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening. |
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| Secondary | Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) | Number of subjects per Tropism status (CCR5 [R5], CXCR4 [X4], Dual Mixed [DM], or Non-reportable/Non-phenotypable [NR/NP]) at Screening (Scr) and at time of treatment failure (Tx fail). Treatment failure defined as insufficient clinical response. HIV-1 RNA viral load <500 copies/ml categorized as below lower limit of quantification (BLQ). Tropism may have been assessed at either the Screening or Baseline visit. The assessment for time of treatment failure is defined as the last on-treatment assessment. | FAS-as treated; N=subjects with TX failure due to insufficient clinical response and who had a tropism assessment at Screening. Subjects with DC prior to timepoint not included; LOCF if no result (viral load too low for analysis). | Posted | | Number | | participants | | Screening through Week 24 | | | | ID | Title | Description |
|---|
| OG000 | Maraviroc QD | Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening. | | OG001 | Maraviroc BID | Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening. |
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| Secondary | Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) | Number of subjects per Tropism status (CCR5 [R5], CXCR4 [X4], Dual Mixed [DM], or Non-reportable/Non-phenotypable [NR/NP]) at Screening (Scr) and at time of treatment failure (Tx fail). Treatment failure defined as insufficient clinical response. HIV-1 RNA viral load <500 copies/ml categorized as below lower limit of quantification (BLQ). Tropism may have been assessed at either the Screening or Baseline visit. The assessment for time of treatment failure is defined as the last on-treatment assessment. | FAS-as treated; N=subjects with TX failure due to insufficient clinical response and who had a tropism assessment at Screening. Subjects with DC prior to timepoint not included; LOCF if no result (viral load too low for analysis). | Posted | | Number | | participants | | Screening through Week 48 | | | | ID | Title | Description |
|---|
| OG000 | Maraviroc QD | Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening. | | OG001 | Maraviroc BID | Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening. |
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| Secondary | Number of Subjects With Treatment Failure at Week 24 by Overall Susceptibility Score (OSS) at Screening | Number of subjects for association between screening resistance and virologic response as determined by treatment failure and OSS at screening. OSS categorized as 0-1, 2-4, >4 (maximum value of 6) and calculated as the sum of the net assessment of in vitro phenotypic and genotypic susceptibility using a binary scoring system (0= reduced susceptibility, 1=susceptible) for each antiretroviral agent in OBT. Higher scores indicate greater susceptibility. | FAS - as treated dual-tropic subjects. Missing values imputed as LOCF. | Posted | | Number | | participants | | Screening, Week 24 | | | | ID | Title | Description |
|---|
| OG000 | Maraviroc QD | Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening. | | OG001 | Maraviroc BID | Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening. | | OG002 | Placebo | |
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| Secondary | Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening | Number of subjects for association between screening resistance and virologic response as determined by treatment failure and OSS at screening. OSS categorized as 0, 1, 2, or ≥3 (maximum value of 6) and calculated as the sum of the net assessment of in vitro phenotypic and genotypic susceptibility using a binary scoring system (0= reduced susceptibility, 1=susceptible) for each antiretroviral agent in OBT. Higher scores indicate greater susceptibility. | FAS - as treated dual-tropic subjects. Missing values imputed as LOCF. | Posted | | Number | | particpants | | Screening, Week48 | | | | ID | Title | Description |
|---|
| OG000 | Maraviroc QD | Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening. | | OG001 | Maraviroc BID | Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening. | | OG002 | Placebo | |
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| Secondary | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Number of subjects with AIDS-defining opportunistic illnesses based on investigator classification guided by a predefined list of clinical Category C Adverse Events per Center for Disease Control (CDC) HIV Classification System. Includes events occurring up to 7 days after last dose of study drug. | FAS - as randomized; N=number of subjects with Category C Adverse Events for maraviroc QD, maraviroc BID, and placebo, respectively. Week 48 results reflect subsequent updates to data originally reported at Week 24. | Posted | | Number | | participants | | Baseline through Week 24 | | | | ID | Title | Description |
|---|
| OG000 | Maraviroc QD | Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening. | | OG001 | Maraviroc BID | Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening. | | OG002 | Placebo | |
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| Secondary | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) | Number of subjects with AIDS-defining opportunistic illnesses based on investigator classification guided by a predefined list of clinical Category C Adverse Events per CDC HIV Classification System. Includes events occurring up to 7 days after last dose of study drug. | FAS - as randomized; N=number of subjects with Category C Adverse Events for maraviroc QD, maraviroc BID, and placebo, respectively. Week 48 results reflect subsequent updates to data originally reported at Week 24. | Posted | | Number | | participants | | Baseline through Week 48 | | | | ID | Title | Description |
|---|
| OG000 | Maraviroc QD | Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening. | | OG001 | Maraviroc BID | Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening. | | OG002 | Placebo | Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening. |
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