HIV Infections
Conditions
Brief summary
Vicriviroc (vye-kri-VYE-rock) is an investigational drug that belongs to a new class of drugs, called C-C chemokine receptor type 5 (CCR5) receptor blockers. This group of drugs blocks one of the ways human immunodeficiency virus (HIV) enters T-cells (the cells that fight infection). The purpose of this 48-week study is to evaluate 2 dose levels of vicriviroc in participants with HIV who have not responded adequately to standard HIV treatments. This study was designed to evaluate the safety and efficacy of doses of vicriviroc, when taken in combination with other HIV drugs, in terms of ability to decrease the level of HIV (viral load) in the blood. The primary objective of the study was to evaluate antiviral efficacy of two doses of Vicriviroc maleate compared to placebo in combination with a protease inhibitor (PI)-containing optimized antiretroviral therapy (ART) regimen in CCR5-tropic HIV infected individuals failing a standard ART regimen.
Detailed description
This is a randomized, double-blind, placebo controlled, parallel-group, multi-center study of vicriviroc maleate in participants with HIV infected with CCR5-tropic virus only for whom standard antiretroviral treatment (ART) has failed. The study will evaluate the antiviral efficacy of two doses of vicriviroc (20 mg once daily (QD) and 30 mg QD) compared with placebo when added to optimized ART therapy. The optimized background regimen will be chosen by the investigator based on results of drug susceptibility tests, history of prior antiretroviral drug use by the participant, and drug toxicity. The background regimen must include at least 3 antiretroviral drugs (not including study drug), one of which must be a ritonavir-boosted protease inhibitor (≥100 mg ritonavir). There will be two interim analyses: when all participants have completed 12 weeks and 24 weeks of treatment, respectively. Based on the balance of safety and efficacy determined in these analyses, a dosage or dosages will be selected for further study in additional registrational trials. The primary efficacy analysis will be conducted when all participants have completed 48 weeks of treatment. After Week 48, participants who meet applicable criteria will be offered open label vicriviroc 30 mg QD, if appropriate, until the sponsor terminates the clinical development of vicriviroc. Additionally, participants who discontinue early from the study prior to Week 48 will be offered re-screening for the open label segment of the study.
Interventions
DRUGVicriviroc 30 mg
Three tablets of vicriviroc 10 mg once daily for 48 weeks (Double-blind Period) or for up to 45 months (Open Label Period).
DRUGVicriviroc 20 mg
Two tablets of vicriviroc 10 mg once daily for 48 weeks.
DRUGPlacebo
Three tablets of placebo once daily for 48 weeks.
DRUGBackground ART Regimen
An open-label ritonavir-boosted optimized background ART regimen containing ≥3 drugs (including a protease inhibitor \[PI\]) selected for each individual study participant by the investigator. The optimized regimens most commonly include new nucleoside analogs (NRTIs) and a PI, usually boosted with concomitant ritonavir.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
There were Double-blind and an Open Label extension period.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult participants with documented HIV infection with no detectable C-X-C Motif Chemokine Receptor 4 (CXCR4) * Prior therapy for ≥3 months with ≥3 classes of currently marketed (US FDA-approved) antiretroviral agents (nucleoside reverse transcriptase inhibitor, NRTIs, non-nucleoside reverse transcriptase inhibitor (NNRTIs), protease inhibitor (PIs), or fusion inhibitors) at any time prior to screening * HIV ribonucleic acid (RNA) ≥1000 copies/mL on a stable ART regimen for ≥6 weeks prior to Screening and ≥8 weeks prior to randomization * ≥1 genotypically documented resistance mutation to a reverse transcriptase (RT) inhibitor and ≥1 primary resistance mutation to a PI * Acceptable hematologic, renal and hepatic laboratory parameters
Exclusion criteria
* No history of previous malignancy (with the exceptions of cutaneous Kaposi's Sarcoma without visceral or mucosal involvement that resolved with highly active antiretroviral therapy (HAART) but without systemic anti-cancer treatment, and basal-cell carcinoma of skin surgically resected with disease-free margins on pathology exam) * Treatment with cytotoxic cancer chemotherapy, * Recurrent seizure, or central nervous system (CNS) condition or drug use predisposing to seizure in the opinion of the investigator * No active acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Log10 Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) at Week 48 of the Double-blind Period | Baseline and Week 48 of the Double-blind Period | HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay. For participants who had HIV RNA below the lower quantification of the Standard assay (LOQ of 400 copies/mL), the AMPLICOR HIV-1.5 UltraSensitive assay was performed. If the HIV RNA measurement was below the lower quantification of the UltraSensitive assay (LOQ of 50 copies/mL), a value of 49 was imputed. If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. If the participants had no subsequent following value or discontinued study treatment before the time point of interest, then the change from baseline was set to zero. Analysis was performed with a variance (ANOVA) model that adjusted for the treatment and stratification factors (intended enfuvirtide (T20) use in current newly-optimized background regimen (OBT) (Y/N) and HIV RNA at Screening (\> or ≤100,000 copies/mL)). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants With HIV RNA <400 Copies/mL at Week 48 of the Double-blind Period | Week 48 of the Double-blind Period | HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay. For participants who had HIV RNA below the lower quantification of the Standard assay (LOQ of 400 copies/mL), the AMPLICOR HIV-1.5 UltraSensitive assay was performed. If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. If the participants had no subsequent following value or discontinued study treatment before the time point of interest, then the change from baseline was set to zero. |
| Participants With a Time to Loss of Virologic Response (TLOVR) Based on 0.5 Log10 Reduction by 48 Weeks of the Double-blind Period | Up to 48 weeks of the Double-blind Period | TLOVR defined as the time from randomization to either: 1. Failure to experience HIV RNA decline of ≥0.5 log10 from Baseline at Week 4, in which case time was set to 0; or 2. Rebound of HIV RNA to within 0.5 log10 of baseline value at any time after maximum suppression. HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay. For participants who had HIV RNA below the lower quantification of the Standard assay (LOQ of 400 c/mL), the AMPLICOR HIV-1.5 UltraSensitive assay was performed. If the HIV RNA measurement was below the lower quantification of the UltraSensitive assay (LOQ of 50 c/mL), a value of 49 was imputed. If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. If the participants had no subsequent following value or discontinued study treatment before the time point of interest, then the change from baseline was set to zero. |
| Change From Baseline in Log10 HIV RNA at Week 12 of the Double-blind Period | Baseline and Week 12 of the Double-blind Period | HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay. For participants who had HIV RNA below the lower quantification of the Standard assay (LOQ of 400 c/mL), the AMPLICOR HIV-1.5 UltraSensitive assay was performed. If the HIV RNA measurement was below the lower quantification of the UltraSensitive assay (LOQ of 50 c/mL), a value of 49 was imputed. If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. Missing values of change from baseline were imputed by the average of immediately preceding and following non-missing values, and in any other cases, missing values were imputed by zero. |
| Change From Baseline in Log10 HIV RNA at Week 24 of the Double-blind Period | Baseline and Week 24 of the Double-blind Period | HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay. For participants who had HIV RNA below the lower quantification of the Standard assay (LOQ of 400 c/mL), the AMPLICOR HIV-1.5 UltraSensitive assay was performed. If the HIV RNA measurement was below the lower quantification of the UltraSensitive assay (LOQ of 50 c/mL), a value of 49 was imputed. If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. Missing values of change from baseline were imputed by the average of immediately preceding and following non-missing values, and in any other cases, missing values were imputed by zero. |
| Change From Baseline CD4 Cells Count at Week 12 of the Double-blind Period | Baseline and Week 12 of the Double-blind Period | Blood was collected and CD4+ cell count assessment was done by flow cytometry. Mean change from baseline in CD4 cell counts was determined. Any missing value was replaced by carrying forward baseline except if the immediately preceding and following value are available, in which case the arithmetic average of the two was used. If more than 1 CD4 count was available during a visit window, the value that was the closest to the time point of interest was used. If more than 1 pre-treatment CD4 value was available at baseline, the arithmetic mean of the 2 CD4 counts was taken. |
| Change From Baseline CD4 Count at Week 24 of the Double-blind Period | Baseline and Week 24 of the Double-blind Period | Blood was collected and CD4+ cell count assessment was done by flow cytometry. Mean change from baseline in CD4 cell counts was determined. Any missing value was replaced by carrying forward baseline except if the immediately preceding and following value are available, in which case the arithmetic average of the two was used. If more than 1 CD4 count was available during a visit window, the value that was the closest to the time point of interest was used. If more than 1 pre-treatment CD4 value was available at baseline, the arithmetic mean of the 2 CD4 counts was taken. |
| Change From Baseline CD4 Count at Week 48 of the Double-blind Period | Baseline and Week 48 of the Double-blind Period | Blood was collected and CD4+ cell count assessment was done by flow cytometry. Mean change from baseline in CD4 cell counts was determined. Any missing value was replaced by carrying forward baseline except if the immediately preceding and following value are available, in which case the arithmetic average of the two was used. If more than 1 CD4 count was available during a visit window, the value that was the closest to the time point of interest was used. If more than 1 pre-treatment CD4 value was available at baseline, the arithmetic mean of the 2 CD4 counts was taken. |
| Change From Baseline CD4 Count at Month 42 of the Open Label Extension | Baseline and Month 42 of the Open Label Period | Blood was collected and CD4+ cell count assessment was done by flow cytometry. Mean change from baseline in CD4 cell counts was determined. Any missing value was replaced by carrying forward baseline except if the immediately preceding and following value are available, in which case the arithmetic average of the two was used. If more than 1 CD4 count was available during a visit window, the value that was the closest to the time point of interest was used. If more than 1 pre-treatment CD4 value was available at baseline, the arithmetic mean of the 2 CD4 counts was taken. After completion of the Double-Blind Period, eligible participants could enroll in the Open Label Period and continue treatment. |
| Participants With <400 Copies/mL HIV RNA at Week 12 of the Double-blind Period | Week 12 of the Double-blind Period | HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay. For participants who had HIV RNA below the lower quantification of the Standard assay (LOQ of 400 copies/mL), the AMPLICOR HIV-1.5 UltraSensitive assay was performed. If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. If the participants had no subsequent following value or discontinued study treatment before the time point of interest, then the change from baseline was set to zero. HIV RNA \<400 copies/mL is a less stringent measure of viral suppression and indicates that a participant responded to treatment. |
| Participants With <400 Copies/mL HIV RNA at Week 24 of the Double-blind Period | Week 24 of the Double-blind Period | HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay. For participants who had HIV RNA below the lower quantification of the Standard assay (LOQ of 400 copies/mL), the AMPLICOR HIV-1.5 UltraSensitive assay was performed. If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. If the participants had no subsequent following value or discontinued study treatment before the time point of interest, then the change from baseline was set to zero. HIV RNA \<400 copies/mL is a less stringent measure of viral suppression and indicates that a participant responded to treatment. |
| Number of Participants With <50, 50 to <400, and ≥400 Copies/mL HIV RNA of the Open Label Extension | Up to 45 months of the Open Label Extension | HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay (the lower quantification, \[LOQ of 400 copies/mL\]) and for HIV RNA below the LOQ, with the AMPLICOR HIV-1.5 UltraSensitive assay. HIV RNA \<400 copies/mL is a less stringent measure of viral suppression (participant responded to treatment). HIV RNA \< 50 copies/mL is a very stringent measure of viral suppression (participant achieved full virologic suppression). If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. Missing value for any reason will be imputed as non-responder except if the immediately preceding and following viral counts are both \<50 copies/mL. Results are shown for Group 1. for participants with baseline HIV RNA \<50 copies/mL, Group 2. baseline HIV RNA 50 to \<400 copies/mL, and Group 3. baseline HIV RNA\>400 copies/mL. |
| Participants With ≥1.0 log10 Change From Baseline HIV RNA at Week 48 of the Double-blind Period | Baseline and 48 Weeks of the Double-blind Period | HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay. For participants who had HIV RNA below the lower quantification of the Standard assay (LOQ of 400 copies/mL), the AMPLICOR HIV-1.5 UltraSensitive assay was performed. If the HIV RNA measurement was below the lower quantification of the UltraSensitive assay (LOQ of 50 copies/mL), a value of 49 was imputed. If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. If the participants had no subsequent following value or discontinued study treatment before the time point of interest, then the change from baseline was set to zero. |
| Participants With <50 Copies/mL HIV RNA at Week 24 of the Double-blind Period | Week 24 of the Double-blind Period | The lower limit of HIV RNA \<50 copies/mL was determined by the UltraSensitive assay. HIV RNA \< 50 copies/mL is a very stringent measure of viral suppression and indicates that a participant achieved full virologic suppression. Missing value for any reason will be imputed as non-responder except if the immediately preceding and following viral counts are both \<50 copies/mL. |
| Participants With <50 Copies/mL HIV RNA at Week 48 of the Double-blind Period | Week 48 of the Double-blind Period | The lower limit of HIV RNA \<50 copies/mL was determined by the UltraSensitive assay. HIV RNA \<50 copies/mL is a very stringent measure of viral suppression and indicates that a participant achieved full virologic suppression. Missing value for any reason were imputed as non-responder except if the immediately preceding and following viral counts are both \<50 copies/mL. |
| Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Events of the Double-blind Period | Up to 48 weeks of the Double-blind Period | All potential AIDS-defining events (ADEs) identified by investigators and the sponsor were submitted with supporting clinical data to an Adjudication Committee of HIV experts. These experts did not participant in the study and reviewed the data without knowledge of treatment assignment. To be analyzed as an ADE, the event required concurrence on the diagnosis by at least two of the three Adjudication Committee members. Their review consisted of available clinical and laboratory data, including relevant radiologic, endoscopic, and pathology assessments, when applicable as well as autopsy reports and/or hospital admission and discharge summaries. An independent radiologist was called upon when necessary. Guidelines for Diagnosis of AIDS-Defining Conditions (CDC's 1993 Revised Classification System for HIV Infection and Expanded Surveillance Case Definition for AIDS Among Adolescents and Adults) was used. |
| Participants With AIDS-defining Events of the Open Label Extension | Up to 45 months of the Open Label Extension | All potential AIDS-defining events (ADEs) identified by investigators and the sponsor were submitted with supporting clinical data to an Adjudication Committee of HIV experts, who did not participant in the study and reviewed the blinded data. Their review consisted of available clinical and laboratory data, including relevant radiologic, endoscopic, and pathology assessments, autopsy reports and/or hospital admission and discharge summaries. An independent radiologist was called upon when necessary. Guidelines for Diagnosis of AIDS-Defining Conditions (CDC's 1993 Revised Classification System for HIV Infection and Expanded Surveillance Case Definition for AIDS Among Adolescents and Adults) was used. To be analyzed as an ADE, the event required concurrence on the diagnosis by at least 2 of 3 Adjudication Committee members. After completion of the Double-blind Period, eligible participants could enroll in the Open Label Period and continue treatment. |
| Time to Occurrence of an AIDS-defining Event of the Double-blind Period | Up to 48 weeks of the Double-blind Period | All potential AIDS-defining events (ADEs) identified by investigators and the sponsor were submitted with supporting clinical data to an independent and blinded Adjudication Committee of HIV experts. To be analyzed as an ADE, the event required concurrence on the diagnosis by at least 2 of the 3 Adjudication Committee members. Their review included available clinical and laboratory data, including relevant radiologic, endoscopic, and pathology assessments, when applicable as well as autopsy reports and/or hospital admission and discharge summaries. An independent radiologist was called upon when necessary. Guidelines for Diagnosis of AIDS-Defining Conditions (CDC's 1993 Revised Classification System for HIV Infection and Expanded Surveillance Case Definition for AIDS Among Adolescents and Adults) was used. |
| Observed Minimum Serum Concentration of Vicriviroc (Cmin) of the Double-blind Period | Two blood samples 2 hours apart on Week 4, Week 12, and Week 24 of the Double-blind Period | Key pharmacokinetic (PK) parameters (maximum plasma concentration \[Cmax\], minimum plasma concentration \[Cmin\], area under the plasma concentration-time curve \[AUC\]) were estimated using a population PK modeling approach based on a two-compartment model with first-order absorption and elimination. Cmin is a measure of the minimum amount of drug in the plasma after the dose is given. Pharmacokinetics studies were not performed with participants receiving Placebo. |
| Observed Maximum (Peak) Plasma Concentration of Vicriviroc (Cmax) of the Double-blind Period | Two blood samples 2 hours apart on Week 4, Week 12, and Week 24 of the Double-blind Period | Key pharmacokinetic (PK) parameters (maximum plasma concentration \[Cmax\], minimum plasma concentration \[Cmin\], area under the plasma concentration-time curve \[AUC\]) were estimated using a population PK modeling approach based on a two-compartment model with first-order absorption and elimination. Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Pharmacokinetics studies were not performed with participants receiving Placebo. |
| Area Under the Plasma Concentration Versus Time Curve of Vicriviroc (AUC) of the Double-blind Period | Two blood samples 2 hours apart on Week 4, Week 12, and Week 24 of the Double-blind Period | Key pharmacokinetic (PK) parameters (maximum plasma concentration \[Cmax\], minimum plasma concentration \[Cmin\], area under the plasma concentration-time curve \[AUC\]) were estimated using a population PK modeling approach based on a two-compartment model with first-order absorption and elimination. AUC is a measure of the mean concentration levels of drug in the plasma after the dose. Pharmacokinetics studies were not performed with participants receiving Placebo. |
| Participants With Detectable Vicriviroc Resistance of the Double-blind Period | Up to 48 weeks of the Double-blind Period | Resistance testing was performed at Baseline and again at the time of virologic failure or study discontinuation using the Phenosense GT assay (Monogram Biosciences, South San Francisco, CA). This assay used a combination of genotypic and phenotypic resistance techniques to determine an overall sensitivity score (OSS). The OSS represents the total number of drugs in the optimized background regimen (OBT) to which the virus was fully susceptible. Partial sensitivity is not counted towards the OSS. VCV susceptibility testing was performed with a maximal percent inhibition (MPI) plateau value of \<85% as a cutoff for resistance. |
| Participants With Detectable C-X-C Chemokine Receptor Type 4 (CXCR4)-Tropic Virus of the Double-blind Period | Up to 48 weeks of the Double-blind Period | Viral tropism was determined using the Monogram Trofile assay and antiviral drug susceptibility was measured by Monogram PhenoSense GT assay, based on both genotypic and phenotypic sensitivity of HIV isolates. The lower limit of sensitivity of the Trofile assay employed in this study for detection of minor X-4 using variants was 5-10%. |
| Participants With Detectable CXCR4-Tropic Virus and Immune Decline (≥50% Fall in CD4 Count From Baseline) of the Double-blind Period | Up to 48 weeks of the Double-blind Period | Viral tropism was determined using the Monogram Trofile assay and antiviral drug susceptibility was measured by Monogram PhenoSense GT assay, based on both genotypic and phenotypic sensitivity of HIV isolates. The lower limit of sensitivity of the Trofile assay employed in this study for detection of minor X-4 using variants was 5-10%. Participants with emergence of CXCR4 tropism who had a concomitant decline in CD4 count by ≥50% below baseline was also computed. |
| Participants With <50 Copies/mL HIV RNA at Week 12 of the Double-blind Period | Week 12 of the Double-blind Period | The lower limit of HIV RNA \<50 copies/mL was determined by the UltraSensitive assay. HIV RNA \<50 copies/mL is a very stringent measure of viral suppression and indicates that a participant achieved full virologic suppression. Missing value for any reason were imputed as non-responder except if the immediately preceding and following viral counts are both \<50 copies/mL. |
Participant flow
Recruitment details
After completing 48 weeks of blinded treatment, participants were offered open-label VCV 30 mg QD in addition to optimized background therapy (OBT). Participants who discontinued before Week 48 of the double-blind segment of the trial for reasons other than adverse events were offered rescreening for the open label extension.
Participants by arm
| Arm | Count |
|---|---|
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen Vicriviroc 30 mg once daily (QD), orally (PO), plus an open-label optimized antiretroviral therapy (ART) regimen containing a ritonavir-boosted protease inhibitor (PI/r) for 48 weeks. | 39 |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. | 40 |
| Double-Blind Period - Placebo Plus an ART Regimen Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. | 37 |
| Total | 116 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-Blind Period | Adverse Event | 0 | 2 | 2 | 0 |
| Double-Blind Period | Protocol Violation | 0 | 0 | 1 | 0 |
| Double-Blind Period | Randomized but Not Treated | 0 | 0 | 2 | 0 |
| Double-Blind Period | Treatment Failure - Virologic Failure defined by investigator | 5 | 3 | 14 | 0 |
| Double-Blind Period | Withdrawal by Subject | 1 | 0 | 0 | 0 |
| Open Label Period | Administrative Reason | 0 | 0 | 0 | 63 |
| Open Label Period | Adverse Event | 0 | 0 | 0 | 2 |
| Open Label Period | Lost to Follow-up | 0 | 0 | 0 | 2 |
| Open Label Period | Progressive Disease (AIDS-Event) | 0 | 0 | 0 | 1 |
| Open Label Period | Protocol Violation | 0 | 0 | 0 | 2 |
| Open Label Period | Treatment Failure - Virologic Failure | 0 | 0 | 0 | 13 |
| Open Label Period | Withdrawal by Subject | 0 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Double-Blind Period - Placebo Plus an ART Regimen | Total |
|---|---|---|---|---|
| Age, Continuous | 44.9 Years STANDARD_DEVIATION 7.3 | 44.0 Years STANDARD_DEVIATION 8 | 45.5 Years STANDARD_DEVIATION 8.8 | 44.8 Years STANDARD_DEVIATION 8 |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 9 Participants | 3 Participants | 8 Participants | 20 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 4 Participants | 8 Participants | 16 Participants |
| Race/Ethnicity, Customized White | 26 Participants | 32 Participants | 21 Participants | 79 Participants |
| Sex: Female, Male Female | 6 Participants | 9 Participants | 11 Participants | 26 Participants |
| Sex: Female, Male Male | 33 Participants | 31 Participants | 26 Participants | 90 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 2 / 40 | 2 / 37 | 1 / 85 |
| other Total, other adverse events | 34 / 39 | 31 / 40 | 29 / 35 | 58 / 85 |
| serious Total, serious adverse events | 4 / 39 | 5 / 40 | 5 / 35 | 13 / 85 |
Outcome results
Primary
Change From Baseline in Log10 Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) at Week 48 of the Double-blind Period
HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay. For participants who had HIV RNA below the lower quantification of the Standard assay (LOQ of 400 copies/mL), the AMPLICOR HIV-1.5 UltraSensitive assay was performed. If the HIV RNA measurement was below the lower quantification of the UltraSensitive assay (LOQ of 50 copies/mL), a value of 49 was imputed. If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. If the participants had no subsequent following value or discontinued study treatment before the time point of interest, then the change from baseline was set to zero. Analysis was performed with a variance (ANOVA) model that adjusted for the treatment and stratification factors (intended enfuvirtide (T20) use in current newly-optimized background regimen (OBT) (Y/N) and HIV RNA at Screening (\> or ≤100,000 copies/mL)).
Time frame: Baseline and Week 48 of the Double-blind Period
Population: The analysis population included all randomized participants who received at least 1 dose of study medication during the Double-blind Period. Participants enrolled in the Open Label Period were not included in this analysis population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Change From Baseline in Log10 Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) at Week 48 of the Double-blind Period | Log10 HIV RNA at Baseline. | 4.52 Log10 copies/mL | Standard Deviation 0.88 |
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Change From Baseline in Log10 Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) at Week 48 of the Double-blind Period | Change from Baseline in Log10 HIV RNA at Week 48. | -1.78 Log10 copies/mL | Standard Deviation 1.31 |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Change From Baseline in Log10 Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) at Week 48 of the Double-blind Period | Log10 HIV RNA at Baseline. | 4.50 Log10 copies/mL | Standard Deviation 0.89 |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Change From Baseline in Log10 Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) at Week 48 of the Double-blind Period | Change from Baseline in Log10 HIV RNA at Week 48. | -1.73 Log10 copies/mL | Standard Deviation 1.31 |
| Double-Blind Period - Placebo Plus an ART Regimen | Change From Baseline in Log10 Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) at Week 48 of the Double-blind Period | Log10 HIV RNA at Baseline. | 4.62 Log10 copies/mL | Standard Deviation 0.79 |
| Double-Blind Period - Placebo Plus an ART Regimen | Change From Baseline in Log10 Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) at Week 48 of the Double-blind Period | Change from Baseline in Log10 HIV RNA at Week 48. | -0.80 Log10 copies/mL | Standard Deviation 1.31 |
p-value: 0.001795% CI: [-1.58, -0.37]ANOVA
p-value: 0.002695% CI: [-1.54, -0.33]ANOVA
Secondary
Area Under the Plasma Concentration Versus Time Curve of Vicriviroc (AUC) of the Double-blind Period
Key pharmacokinetic (PK) parameters (maximum plasma concentration \[Cmax\], minimum plasma concentration \[Cmin\], area under the plasma concentration-time curve \[AUC\]) were estimated using a population PK modeling approach based on a two-compartment model with first-order absorption and elimination. AUC is a measure of the mean concentration levels of drug in the plasma after the dose. Pharmacokinetics studies were not performed with participants receiving Placebo.
Time frame: Two blood samples 2 hours apart on Week 4, Week 12, and Week 24 of the Double-blind Period
Population: The analysis population included all randomized participants who received at least 1 dose of Vicriviroc during the Double-blind Period. Pharmacokinetics studies were not performed with participants receiving Placebo. Participants enrolled in the Open Label Period were not included in this analysis population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Area Under the Plasma Concentration Versus Time Curve of Vicriviroc (AUC) of the Double-blind Period | 5795.62 hr*ng/mL | Standard Deviation 1906.59 |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Area Under the Plasma Concentration Versus Time Curve of Vicriviroc (AUC) of the Double-blind Period | 4314.88 hr*ng/mL | Standard Deviation 1497.7 |
Secondary
Change From Baseline CD4 Cells Count at Week 12 of the Double-blind Period
Blood was collected and CD4+ cell count assessment was done by flow cytometry. Mean change from baseline in CD4 cell counts was determined. Any missing value was replaced by carrying forward baseline except if the immediately preceding and following value are available, in which case the arithmetic average of the two was used. If more than 1 CD4 count was available during a visit window, the value that was the closest to the time point of interest was used. If more than 1 pre-treatment CD4 value was available at baseline, the arithmetic mean of the 2 CD4 counts was taken.
Time frame: Baseline and Week 12 of the Double-blind Period
Population: The analysis population included all randomized participants who received at least 1 dose of study medication and had baseline and Week 12 endpoint measurements during the Double-blind Period. Participants enrolled in the Open Label Period were not included in this analysis population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Change From Baseline CD4 Cells Count at Week 12 of the Double-blind Period | CD4 Cells Count at Baseline | 202.23 Cells/mm^3 | Standard Deviation 159.22 |
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Change From Baseline CD4 Cells Count at Week 12 of the Double-blind Period | Change from Baseline CD4 Cells Count at Week 12 | 109.85 Cells/mm^3 | Standard Deviation 110.23 |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Change From Baseline CD4 Cells Count at Week 12 of the Double-blind Period | CD4 Cells Count at Baseline | 202.10 Cells/mm^3 | Standard Deviation 144.47 |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Change From Baseline CD4 Cells Count at Week 12 of the Double-blind Period | Change from Baseline CD4 Cells Count at Week 12 | 94.46 Cells/mm^3 | Standard Deviation 110.31 |
| Double-Blind Period - Placebo Plus an ART Regimen | Change From Baseline CD4 Cells Count at Week 12 of the Double-blind Period | Change from Baseline CD4 Cells Count at Week 12 | 52.09 Cells/mm^3 | Standard Deviation 110.21 |
| Double-Blind Period - Placebo Plus an ART Regimen | Change From Baseline CD4 Cells Count at Week 12 of the Double-blind Period | CD4 Cells Count at Baseline | 214.41 Cells/mm^3 | Standard Deviation 185.62 |
p-value: 0.026495% CI: [6.9, 108.61]ANOVA
p-value: 0.10295% CI: [-8.55, 93.28]ANOVA
Secondary
Change From Baseline CD4 Count at Month 42 of the Open Label Extension
Blood was collected and CD4+ cell count assessment was done by flow cytometry. Mean change from baseline in CD4 cell counts was determined. Any missing value was replaced by carrying forward baseline except if the immediately preceding and following value are available, in which case the arithmetic average of the two was used. If more than 1 CD4 count was available during a visit window, the value that was the closest to the time point of interest was used. If more than 1 pre-treatment CD4 value was available at baseline, the arithmetic mean of the 2 CD4 counts was taken. After completion of the Double-Blind Period, eligible participants could enroll in the Open Label Period and continue treatment.
Time frame: Baseline and Month 42 of the Open Label Period
Population: The analysis population included all randomized participants who received at least 1 dose of study medication and had baseline and Month 42 endpoint measurements during the Open Label Period. Participants enrolled in the Double-blind Period were not included in this analysis population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Change From Baseline CD4 Count at Month 42 of the Open Label Extension | CD4 Count at Baseline (Open Label Extension). | 366.16 Cells/mm^3 | Standard Deviation 191.86 |
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Change From Baseline CD4 Count at Month 42 of the Open Label Extension | Change from Baseline CD4 Count at Month 42. | -78.67 Cells/mm^3 | Standard Deviation 283.28 |
Secondary
Change From Baseline CD4 Count at Week 24 of the Double-blind Period
Blood was collected and CD4+ cell count assessment was done by flow cytometry. Mean change from baseline in CD4 cell counts was determined. Any missing value was replaced by carrying forward baseline except if the immediately preceding and following value are available, in which case the arithmetic average of the two was used. If more than 1 CD4 count was available during a visit window, the value that was the closest to the time point of interest was used. If more than 1 pre-treatment CD4 value was available at baseline, the arithmetic mean of the 2 CD4 counts was taken.
Time frame: Baseline and Week 24 of the Double-blind Period
Population: The analysis population included all randomized participants who received at least 1 dose of study medication and had baseline and Week 24 endpoint measurements during the Double-blind Period. Participants enrolled in the Open Label Period were not included in this analysis population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Change From Baseline CD4 Count at Week 24 of the Double-blind Period | CD4 Count at Baseline. | 202.23 Cells/mm^3 | Standard Deviation 159.22 |
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Change From Baseline CD4 Count at Week 24 of the Double-blind Period | Change from Baseline CD4 Count at Week 24. | 97.58 Cells/mm^3 | Standard Deviation 113.66 |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Change From Baseline CD4 Count at Week 24 of the Double-blind Period | CD4 Count at Baseline. | 202.10 Cells/mm^3 | Standard Deviation 144.47 |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Change From Baseline CD4 Count at Week 24 of the Double-blind Period | Change from Baseline CD4 Count at Week 24. | 103.58 Cells/mm^3 | Standard Deviation 113.74 |
| Double-Blind Period - Placebo Plus an ART Regimen | Change From Baseline CD4 Count at Week 24 of the Double-blind Period | CD4 Count at Baseline. | 214.41 Cells/mm^3 | Standard Deviation 185.62 |
| Double-Blind Period - Placebo Plus an ART Regimen | Change From Baseline CD4 Count at Week 24 of the Double-blind Period | Change from Baseline CD4 Count at Week 24. | 59.46 Cells/mm^3 | Standard Deviation 113.64 |
p-value: 0.152595% CI: [-14.32, 90.56]ANOVA
p-value: 0.098795% CI: [-8.38, 96.61]ANOVA
Secondary
Change From Baseline CD4 Count at Week 48 of the Double-blind Period
Blood was collected and CD4+ cell count assessment was done by flow cytometry. Mean change from baseline in CD4 cell counts was determined. Any missing value was replaced by carrying forward baseline except if the immediately preceding and following value are available, in which case the arithmetic average of the two was used. If more than 1 CD4 count was available during a visit window, the value that was the closest to the time point of interest was used. If more than 1 pre-treatment CD4 value was available at baseline, the arithmetic mean of the 2 CD4 counts was taken.
Time frame: Baseline and Week 48 of the Double-blind Period
Population: The analysis population included all randomized participants who received at least 1 dose of study medication and had baseline and Week 48 endpoint measurements during the Double-blind Period. Participants enrolled in the Open Label Period were not included in this analysis population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Change From Baseline CD4 Count at Week 48 of the Double-blind Period | CD4 Count at Baseline. | 202.23 Cells/mm^3 | Standard Deviation 159.22 |
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Change From Baseline CD4 Count at Week 48 of the Double-blind Period | Change from Baseline CD4 Count at Week 48. | 102.12 Cells/mm^3 | Standard Deviation 141.68 |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Change From Baseline CD4 Count at Week 48 of the Double-blind Period | CD4 Count at Baseline. | 202.10 Cells/mm^3 | Standard Deviation 144.47 |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Change From Baseline CD4 Count at Week 48 of the Double-blind Period | Change from Baseline CD4 Count at Week 48. | 133.88 Cells/mm^3 | Standard Deviation 141.79 |
| Double-Blind Period - Placebo Plus an ART Regimen | Change From Baseline CD4 Count at Week 48 of the Double-blind Period | CD4 Count at Baseline. | 214.41 Cells/mm^3 | Standard Deviation 185.62 |
| Double-Blind Period - Placebo Plus an ART Regimen | Change From Baseline CD4 Count at Week 48 of the Double-blind Period | Change from Baseline CD4 Count at Week 48. | 64.80 Cells/mm^3 | Standard Deviation 141.65 |
p-value: 0.260395% CI: [-28.05, 102.68]ANOVA
p-value: 0.038795% CI: [3.64, 134.52]ANOVA
Secondary
Change From Baseline in Log10 HIV RNA at Week 12 of the Double-blind Period
HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay. For participants who had HIV RNA below the lower quantification of the Standard assay (LOQ of 400 c/mL), the AMPLICOR HIV-1.5 UltraSensitive assay was performed. If the HIV RNA measurement was below the lower quantification of the UltraSensitive assay (LOQ of 50 c/mL), a value of 49 was imputed. If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. Missing values of change from baseline were imputed by the average of immediately preceding and following non-missing values, and in any other cases, missing values were imputed by zero.
Time frame: Baseline and Week 12 of the Double-blind Period
Population: The analysis population included all randomized participants who received at least 1 dose of study medication during the Double-blind Period. Participants enrolled in the Open Label Period were not included in this analysis population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Change From Baseline in Log10 HIV RNA at Week 12 of the Double-blind Period | Log10 HIV RNA at Baseline. | 4.52 Log10 copies/mL | Standard Deviation 0.88 |
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Change From Baseline in Log10 HIV RNA at Week 12 of the Double-blind Period | Change from Baseline in Log10 HIV RNA at Week 12. | -2.11 Log10 copies/mL | Standard Deviation 1.14 |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Change From Baseline in Log10 HIV RNA at Week 12 of the Double-blind Period | Log10 HIV RNA at Baseline. | 4.50 Log10 copies/mL | Standard Deviation 0.89 |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Change From Baseline in Log10 HIV RNA at Week 12 of the Double-blind Period | Change from Baseline in Log10 HIV RNA at Week 12. | -1.94 Log10 copies/mL | Standard Deviation 1.14 |
| Double-Blind Period - Placebo Plus an ART Regimen | Change From Baseline in Log10 HIV RNA at Week 12 of the Double-blind Period | Log10 HIV RNA at Baseline. | 4.62 Log10 copies/mL | Standard Deviation 0.79 |
| Double-Blind Period - Placebo Plus an ART Regimen | Change From Baseline in Log10 HIV RNA at Week 12 of the Double-blind Period | Change from Baseline in Log10 HIV RNA at Week 12. | -1.11 Log10 copies/mL | Standard Deviation 1.14 |
p-value: 0.000295% CI: [-1.53, -0.48]ANOVA
p-value: 0.00295% CI: [-1.36, -0.31]ANOVA
Secondary
Change From Baseline in Log10 HIV RNA at Week 24 of the Double-blind Period
HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay. For participants who had HIV RNA below the lower quantification of the Standard assay (LOQ of 400 c/mL), the AMPLICOR HIV-1.5 UltraSensitive assay was performed. If the HIV RNA measurement was below the lower quantification of the UltraSensitive assay (LOQ of 50 c/mL), a value of 49 was imputed. If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. Missing values of change from baseline were imputed by the average of immediately preceding and following non-missing values, and in any other cases, missing values were imputed by zero.
Time frame: Baseline and Week 24 of the Double-blind Period
Population: The analysis population included all randomized participants who received at least 1 dose of study medication during the Double-blind Period. Participants enrolled in the Open Label Period were not included in this analysis population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Change From Baseline in Log10 HIV RNA at Week 24 of the Double-blind Period | Log10 HIV RNA at Baseline. | 4.52 Log10 copies/mL | Standard Deviation 0.88 |
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Change From Baseline in Log10 HIV RNA at Week 24 of the Double-blind Period | Change from Baseline in Log10 HIV RNA at Week 24. | -2.07 Log10 copies/mL | Standard Deviation 1.28 |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Change From Baseline in Log10 HIV RNA at Week 24 of the Double-blind Period | Log10 HIV RNA at Baseline. | 4.50 Log10 copies/mL | Standard Deviation 0.89 |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Change From Baseline in Log10 HIV RNA at Week 24 of the Double-blind Period | Change from Baseline in Log10 HIV RNA at Week 24. | -2.04 Log10 copies/mL | Standard Deviation 1.28 |
| Double-Blind Period - Placebo Plus an ART Regimen | Change From Baseline in Log10 HIV RNA at Week 24 of the Double-blind Period | Log10 HIV RNA at Baseline. | 4.62 Log10 copies/mL | Standard Deviation 0.79 |
| Double-Blind Period - Placebo Plus an ART Regimen | Change From Baseline in Log10 HIV RNA at Week 24 of the Double-blind Period | Change from Baseline in Log10 HIV RNA at Week 24. | -0.96 Log10 copies/mL | Standard Deviation 1.28 |
p-value: 0.000395% CI: [-1.69, -0.51]ANOVA
p-value: 0.000495% CI: [-1.66, -0.49]ANOVA
Secondary
Number of Participants With <50, 50 to <400, and ≥400 Copies/mL HIV RNA of the Open Label Extension
HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay (the lower quantification, \[LOQ of 400 copies/mL\]) and for HIV RNA below the LOQ, with the AMPLICOR HIV-1.5 UltraSensitive assay. HIV RNA \<400 copies/mL is a less stringent measure of viral suppression (participant responded to treatment). HIV RNA \< 50 copies/mL is a very stringent measure of viral suppression (participant achieved full virologic suppression). If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. Missing value for any reason will be imputed as non-responder except if the immediately preceding and following viral counts are both \<50 copies/mL. Results are shown for Group 1. for participants with baseline HIV RNA \<50 copies/mL, Group 2. baseline HIV RNA 50 to \<400 copies/mL, and Group 3. baseline HIV RNA\>400 copies/mL.
Time frame: Up to 45 months of the Open Label Extension
Population: The analysis population included all randomized participants who received at least 1 dose of study medication during the Open Label Period. Participants enrolled in the Double-blind Period were not included in this analysis population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Number of Participants With <50, 50 to <400, and ≥400 Copies/mL HIV RNA of the Open Label Extension | Group 2. Last RNA 50 to <400 copies/mL | 2 Participants |
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Number of Participants With <50, 50 to <400, and ≥400 Copies/mL HIV RNA of the Open Label Extension | Group 2. Last RNA ≥400 copies/mL | 3 Participants |
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Number of Participants With <50, 50 to <400, and ≥400 Copies/mL HIV RNA of the Open Label Extension | Group 3. Baseline for RNA ≥400 copies/mL | 27 Participants |
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Number of Participants With <50, 50 to <400, and ≥400 Copies/mL HIV RNA of the Open Label Extension | Group 1. Baseline for RNA <50 copies/mL | 48 Participants |
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Number of Participants With <50, 50 to <400, and ≥400 Copies/mL HIV RNA of the Open Label Extension | Group 1. Last RNA <50 copies/mL | 42 Participants |
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Number of Participants With <50, 50 to <400, and ≥400 Copies/mL HIV RNA of the Open Label Extension | Group 1. Last RNA 50 to <400 copies/mL | 5 Participants |
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Number of Participants With <50, 50 to <400, and ≥400 Copies/mL HIV RNA of the Open Label Extension | Group 1. Last RNA ≥400 copies/mL | 1 Participants |
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Number of Participants With <50, 50 to <400, and ≥400 Copies/mL HIV RNA of the Open Label Extension | Group 2. Baseline for RNA 50 to <400 copies/mL | 10 Participants |
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Number of Participants With <50, 50 to <400, and ≥400 Copies/mL HIV RNA of the Open Label Extension | Group 2. Last RNA <50 copies/mL | 5 Participants |
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Number of Participants With <50, 50 to <400, and ≥400 Copies/mL HIV RNA of the Open Label Extension | Group 3. Last RNA <50 copies/mL | 10 Participants |
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Number of Participants With <50, 50 to <400, and ≥400 Copies/mL HIV RNA of the Open Label Extension | Group 3. Last RNA 50 to <400 copies/mL | 0 Participants |
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Number of Participants With <50, 50 to <400, and ≥400 Copies/mL HIV RNA of the Open Label Extension | Group 3. Last RNA ≥400 copies/mL | 15 Participants |
Secondary
Observed Maximum (Peak) Plasma Concentration of Vicriviroc (Cmax) of the Double-blind Period
Key pharmacokinetic (PK) parameters (maximum plasma concentration \[Cmax\], minimum plasma concentration \[Cmin\], area under the plasma concentration-time curve \[AUC\]) were estimated using a population PK modeling approach based on a two-compartment model with first-order absorption and elimination. Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Pharmacokinetics studies were not performed with participants receiving Placebo.
Time frame: Two blood samples 2 hours apart on Week 4, Week 12, and Week 24 of the Double-blind Period
Population: The analysis population included all randomized participants who received at least 1 dose of Vicriviroc during the Double-blind Period. Pharmacokinetics studies were not performed with participants receiving Placebo. Participants enrolled in the Open Label Period were not included in this analysis population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Observed Maximum (Peak) Plasma Concentration of Vicriviroc (Cmax) of the Double-blind Period | 316.21 ng/mL | Standard Deviation 84.41 |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Observed Maximum (Peak) Plasma Concentration of Vicriviroc (Cmax) of the Double-blind Period | 229.33 ng/mL | Standard Deviation 61.74 |
Secondary
Observed Minimum Serum Concentration of Vicriviroc (Cmin) of the Double-blind Period
Key pharmacokinetic (PK) parameters (maximum plasma concentration \[Cmax\], minimum plasma concentration \[Cmin\], area under the plasma concentration-time curve \[AUC\]) were estimated using a population PK modeling approach based on a two-compartment model with first-order absorption and elimination. Cmin is a measure of the minimum amount of drug in the plasma after the dose is given. Pharmacokinetics studies were not performed with participants receiving Placebo.
Time frame: Two blood samples 2 hours apart on Week 4, Week 12, and Week 24 of the Double-blind Period
Population: The analysis population included all randomized participants who received at least 1 dose of Vicriviroc during the Double-blind Period. Pharmacokinetics studies were not performed with participants receiving Placebo. Participants enrolled in the Open Label Period were not included in this analysis population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Observed Minimum Serum Concentration of Vicriviroc (Cmin) of the Double-blind Period | 206.56 ng/mL | Standard Deviation 76.82 |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Observed Minimum Serum Concentration of Vicriviroc (Cmin) of the Double-blind Period | 156.95 ng/mL | Standard Deviation 62.17 |
Secondary
Participants With ≥1.0 log10 Change From Baseline HIV RNA at Week 48 of the Double-blind Period
HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay. For participants who had HIV RNA below the lower quantification of the Standard assay (LOQ of 400 copies/mL), the AMPLICOR HIV-1.5 UltraSensitive assay was performed. If the HIV RNA measurement was below the lower quantification of the UltraSensitive assay (LOQ of 50 copies/mL), a value of 49 was imputed. If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. If the participants had no subsequent following value or discontinued study treatment before the time point of interest, then the change from baseline was set to zero.
Time frame: Baseline and 48 Weeks of the Double-blind Period
Population: The analysis population included all randomized participants who received at least 1 dose of study medication during the Double-blind Period. Participants enrolled in the Open Label Period were not included in this analysis population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Participants With ≥1.0 log10 Change From Baseline HIV RNA at Week 48 of the Double-blind Period | 26 Participants |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Participants With ≥1.0 log10 Change From Baseline HIV RNA at Week 48 of the Double-blind Period | 25 Participants |
| Double-Blind Period - Placebo Plus an ART Regimen | Participants With ≥1.0 log10 Change From Baseline HIV RNA at Week 48 of the Double-blind Period | 12 Participants |
p-value: 0.0052Cochran-Mantel-Haenszel
p-value: 0.019Cochran-Mantel-Haenszel
Secondary
Participants With <400 Copies/mL HIV RNA at Week 12 of the Double-blind Period
HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay. For participants who had HIV RNA below the lower quantification of the Standard assay (LOQ of 400 copies/mL), the AMPLICOR HIV-1.5 UltraSensitive assay was performed. If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. If the participants had no subsequent following value or discontinued study treatment before the time point of interest, then the change from baseline was set to zero. HIV RNA \<400 copies/mL is a less stringent measure of viral suppression and indicates that a participant responded to treatment.
Time frame: Week 12 of the Double-blind Period
Population: The analysis population included all randomized participants who received at least 1 dose of study medication during the Double-blind Period. Participants enrolled in the Open Label Period were not included in this analysis population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Participants With <400 Copies/mL HIV RNA at Week 12 of the Double-blind Period | 28 Participants |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Participants With <400 Copies/mL HIV RNA at Week 12 of the Double-blind Period | 25 Participants |
| Double-Blind Period - Placebo Plus an ART Regimen | Participants With <400 Copies/mL HIV RNA at Week 12 of the Double-blind Period | 14 Participants |
p-value: 0.0031Cochran-Mantel-Haenszel
p-value: 0.048Cochran-Mantel-Haenszel
Secondary
Participants With <400 Copies/mL HIV RNA at Week 24 of the Double-blind Period
HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay. For participants who had HIV RNA below the lower quantification of the Standard assay (LOQ of 400 copies/mL), the AMPLICOR HIV-1.5 UltraSensitive assay was performed. If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. If the participants had no subsequent following value or discontinued study treatment before the time point of interest, then the change from baseline was set to zero. HIV RNA \<400 copies/mL is a less stringent measure of viral suppression and indicates that a participant responded to treatment.
Time frame: Week 24 of the Double-blind Period
Population: The analysis population included all randomized participants who received at least 1 dose of study medication during the Double-blind Period. Participants enrolled in the Open Label Period were not included in this analysis population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Participants With <400 Copies/mL HIV RNA at Week 24 of the Double-blind Period | 28 Participants |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Participants With <400 Copies/mL HIV RNA at Week 24 of the Double-blind Period | 29 Participants |
| Double-Blind Period - Placebo Plus an ART Regimen | Participants With <400 Copies/mL HIV RNA at Week 24 of the Double-blind Period | 12 Participants |
p-value: 0.0009Cochran-Mantel-Haenszel
p-value: 0.0009Cochran-Mantel-Haenszel
Secondary
Participants With <50 Copies/mL HIV RNA at Week 12 of the Double-blind Period
The lower limit of HIV RNA \<50 copies/mL was determined by the UltraSensitive assay. HIV RNA \<50 copies/mL is a very stringent measure of viral suppression and indicates that a participant achieved full virologic suppression. Missing value for any reason were imputed as non-responder except if the immediately preceding and following viral counts are both \<50 copies/mL.
Time frame: Week 12 of the Double-blind Period
Population: The analysis population included all randomized participants who received at least 1 dose of study medication during the Double-blind Period. Participants enrolled in the Open Label Period were not included in this analysis population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Participants With <50 Copies/mL HIV RNA at Week 12 of the Double-blind Period | 18 Participants |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Participants With <50 Copies/mL HIV RNA at Week 12 of the Double-blind Period | 17 Participants |
| Double-Blind Period - Placebo Plus an ART Regimen | Participants With <50 Copies/mL HIV RNA at Week 12 of the Double-blind Period | 8 Participants |
p-value: 0.0225Cochran-Mantel-Haenszel
p-value: 0.0582Cochran-Mantel-Haenszel
Secondary
Participants With <50 Copies/mL HIV RNA at Week 24 of the Double-blind Period
The lower limit of HIV RNA \<50 copies/mL was determined by the UltraSensitive assay. HIV RNA \< 50 copies/mL is a very stringent measure of viral suppression and indicates that a participant achieved full virologic suppression. Missing value for any reason will be imputed as non-responder except if the immediately preceding and following viral counts are both \<50 copies/mL.
Time frame: Week 24 of the Double-blind Period
Population: The analysis population included all randomized participants who received at least 1 dose of study medication during the Double-blind Period. Participants enrolled in the Open Label Period were not included in this analysis population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Participants With <50 Copies/mL HIV RNA at Week 24 of the Double-blind Period | 25 Participants |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Participants With <50 Copies/mL HIV RNA at Week 24 of the Double-blind Period | 23 Participants |
| Double-Blind Period - Placebo Plus an ART Regimen | Participants With <50 Copies/mL HIV RNA at Week 24 of the Double-blind Period | 9 Participants |
p-value: 0.0009Cochran-Mantel-Haenszel
p-value: 0.0038Cochran-Mantel-Haenszel
Secondary
Participants With <50 Copies/mL HIV RNA at Week 48 of the Double-blind Period
The lower limit of HIV RNA \<50 copies/mL was determined by the UltraSensitive assay. HIV RNA \<50 copies/mL is a very stringent measure of viral suppression and indicates that a participant achieved full virologic suppression. Missing value for any reason were imputed as non-responder except if the immediately preceding and following viral counts are both \<50 copies/mL.
Time frame: Week 48 of the Double-blind Period
Population: The analysis population included all randomized participants who received at least 1 dose of study medication during the Double-blind Period. Participants enrolled in the Open Label Period were not included in this analysis population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Participants With <50 Copies/mL HIV RNA at Week 48 of the Double-blind Period | 22 Participants |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Participants With <50 Copies/mL HIV RNA at Week 48 of the Double-blind Period | 21 Participants |
| Double-Blind Period - Placebo Plus an ART Regimen | Participants With <50 Copies/mL HIV RNA at Week 48 of the Double-blind Period | 5 Participants |
p-value: 0.0002Cochran-Mantel-Haenszel
p-value: 0.0004Cochran-Mantel-Haenszel
Secondary
Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Events of the Double-blind Period
All potential AIDS-defining events (ADEs) identified by investigators and the sponsor were submitted with supporting clinical data to an Adjudication Committee of HIV experts. These experts did not participant in the study and reviewed the data without knowledge of treatment assignment. To be analyzed as an ADE, the event required concurrence on the diagnosis by at least two of the three Adjudication Committee members. Their review consisted of available clinical and laboratory data, including relevant radiologic, endoscopic, and pathology assessments, when applicable as well as autopsy reports and/or hospital admission and discharge summaries. An independent radiologist was called upon when necessary. Guidelines for Diagnosis of AIDS-Defining Conditions (CDC's 1993 Revised Classification System for HIV Infection and Expanded Surveillance Case Definition for AIDS Among Adolescents and Adults) was used.
Time frame: Up to 48 weeks of the Double-blind Period
Population: The analysis population included all randomized participants who received at least 1 dose of study medication during the Double-blind Period. Participants enrolled in the Open Label Period were not included in this analysis population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Events of the Double-blind Period | 0 Participants |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Events of the Double-blind Period | 0 Participants |
| Double-Blind Period - Placebo Plus an ART Regimen | Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Events of the Double-blind Period | 1 Participants |
Secondary
Participants With AIDS-defining Events of the Open Label Extension
All potential AIDS-defining events (ADEs) identified by investigators and the sponsor were submitted with supporting clinical data to an Adjudication Committee of HIV experts, who did not participant in the study and reviewed the blinded data. Their review consisted of available clinical and laboratory data, including relevant radiologic, endoscopic, and pathology assessments, autopsy reports and/or hospital admission and discharge summaries. An independent radiologist was called upon when necessary. Guidelines for Diagnosis of AIDS-Defining Conditions (CDC's 1993 Revised Classification System for HIV Infection and Expanded Surveillance Case Definition for AIDS Among Adolescents and Adults) was used. To be analyzed as an ADE, the event required concurrence on the diagnosis by at least 2 of 3 Adjudication Committee members. After completion of the Double-blind Period, eligible participants could enroll in the Open Label Period and continue treatment.
Time frame: Up to 45 months of the Open Label Extension
Population: The analysis population included all randomized participants who received at least 1 dose of study medication during the Open Label Period. Participants enrolled in the Double-blind Period were not included in this analysis population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Participants With AIDS-defining Events of the Open Label Extension | 1 Participants |
Secondary
Participants With a Time to Loss of Virologic Response (TLOVR) Based on 0.5 Log10 Reduction by 48 Weeks of the Double-blind Period
TLOVR defined as the time from randomization to either: 1. Failure to experience HIV RNA decline of ≥0.5 log10 from Baseline at Week 4, in which case time was set to 0; or 2. Rebound of HIV RNA to within 0.5 log10 of baseline value at any time after maximum suppression. HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay. For participants who had HIV RNA below the lower quantification of the Standard assay (LOQ of 400 c/mL), the AMPLICOR HIV-1.5 UltraSensitive assay was performed. If the HIV RNA measurement was below the lower quantification of the UltraSensitive assay (LOQ of 50 c/mL), a value of 49 was imputed. If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. If the participants had no subsequent following value or discontinued study treatment before the time point of interest, then the change from baseline was set to zero.
Time frame: Up to 48 weeks of the Double-blind Period
Population: The analysis population included all randomized participants who received at least 1 dose of study medication during the Double-blind Period. Participants enrolled in the Open Label Period were not included in this analysis population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Participants With a Time to Loss of Virologic Response (TLOVR) Based on 0.5 Log10 Reduction by 48 Weeks of the Double-blind Period | Participants with Sustained ≥0.5 Log10 Reduction by Week 4 | 31 Participants |
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Participants With a Time to Loss of Virologic Response (TLOVR) Based on 0.5 Log10 Reduction by 48 Weeks of the Double-blind Period | Participants with Rebound by Week 12 | 1 Participants |
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Participants With a Time to Loss of Virologic Response (TLOVR) Based on 0.5 Log10 Reduction by 48 Weeks of the Double-blind Period | Participants with Rebound by Week 24 | 2 Participants |
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Participants With a Time to Loss of Virologic Response (TLOVR) Based on 0.5 Log10 Reduction by 48 Weeks of the Double-blind Period | Participants with Rebound after Week 24 | 1 Participants |
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Participants With a Time to Loss of Virologic Response (TLOVR) Based on 0.5 Log10 Reduction by 48 Weeks of the Double-blind Period | Participants Suppressed through Week 48 | 27 Participants |
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Participants With a Time to Loss of Virologic Response (TLOVR) Based on 0.5 Log10 Reduction by 48 Weeks of the Double-blind Period | Participants with No ≥0.5 Log10 Reduction by Week 4 | 1 Participants |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Participants With a Time to Loss of Virologic Response (TLOVR) Based on 0.5 Log10 Reduction by 48 Weeks of the Double-blind Period | Participants with No ≥0.5 Log10 Reduction by Week 4 | 2 Participants |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Participants With a Time to Loss of Virologic Response (TLOVR) Based on 0.5 Log10 Reduction by 48 Weeks of the Double-blind Period | Participants with Sustained ≥0.5 Log10 Reduction by Week 4 | 32 Participants |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Participants With a Time to Loss of Virologic Response (TLOVR) Based on 0.5 Log10 Reduction by 48 Weeks of the Double-blind Period | Participants with Rebound after Week 24 | 1 Participants |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Participants With a Time to Loss of Virologic Response (TLOVR) Based on 0.5 Log10 Reduction by 48 Weeks of the Double-blind Period | Participants Suppressed through Week 48 | 29 Participants |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Participants With a Time to Loss of Virologic Response (TLOVR) Based on 0.5 Log10 Reduction by 48 Weeks of the Double-blind Period | Participants with Rebound by Week 12 | 1 Participants |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Participants With a Time to Loss of Virologic Response (TLOVR) Based on 0.5 Log10 Reduction by 48 Weeks of the Double-blind Period | Participants with Rebound by Week 24 | 1 Participants |
| Double-Blind Period - Placebo Plus an ART Regimen | Participants With a Time to Loss of Virologic Response (TLOVR) Based on 0.5 Log10 Reduction by 48 Weeks of the Double-blind Period | Participants with Rebound by Week 12 | 1 Participants |
| Double-Blind Period - Placebo Plus an ART Regimen | Participants With a Time to Loss of Virologic Response (TLOVR) Based on 0.5 Log10 Reduction by 48 Weeks of the Double-blind Period | Participants with Rebound by Week 24 | 1 Participants |
| Double-Blind Period - Placebo Plus an ART Regimen | Participants With a Time to Loss of Virologic Response (TLOVR) Based on 0.5 Log10 Reduction by 48 Weeks of the Double-blind Period | Participants with No ≥0.5 Log10 Reduction by Week 4 | 3 Participants |
| Double-Blind Period - Placebo Plus an ART Regimen | Participants With a Time to Loss of Virologic Response (TLOVR) Based on 0.5 Log10 Reduction by 48 Weeks of the Double-blind Period | Participants with Rebound after Week 24 | 1 Participants |
| Double-Blind Period - Placebo Plus an ART Regimen | Participants With a Time to Loss of Virologic Response (TLOVR) Based on 0.5 Log10 Reduction by 48 Weeks of the Double-blind Period | Participants with Sustained ≥0.5 Log10 Reduction by Week 4 | 15 Participants |
| Double-Blind Period - Placebo Plus an ART Regimen | Participants With a Time to Loss of Virologic Response (TLOVR) Based on 0.5 Log10 Reduction by 48 Weeks of the Double-blind Period | Participants Suppressed through Week 48 | 12 Participants |
Secondary
Participants With Detectable C-X-C Chemokine Receptor Type 4 (CXCR4)-Tropic Virus of the Double-blind Period
Viral tropism was determined using the Monogram Trofile assay and antiviral drug susceptibility was measured by Monogram PhenoSense GT assay, based on both genotypic and phenotypic sensitivity of HIV isolates. The lower limit of sensitivity of the Trofile assay employed in this study for detection of minor X-4 using variants was 5-10%.
Time frame: Up to 48 weeks of the Double-blind Period
Population: The analysis population included all randomized participants who received at least 1 dose of study medication during the Double-blind Period. Participants enrolled in the Open Label Period were not included in this analysis population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Participants With Detectable C-X-C Chemokine Receptor Type 4 (CXCR4)-Tropic Virus of the Double-blind Period | Participants With detectable CV with other virologic failures | 8 Participants |
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Participants With Detectable C-X-C Chemokine Receptor Type 4 (CXCR4)-Tropic Virus of the Double-blind Period | Participants With detectable CV (on study drug) | 9 Participants |
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Participants With Detectable C-X-C Chemokine Receptor Type 4 (CXCR4)-Tropic Virus of the Double-blind Period | Participants With detectable CV anytime who discontinued | 4 Participants |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Participants With Detectable C-X-C Chemokine Receptor Type 4 (CXCR4)-Tropic Virus of the Double-blind Period | Participants With detectable CV with other virologic failures | 7 Participants |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Participants With Detectable C-X-C Chemokine Receptor Type 4 (CXCR4)-Tropic Virus of the Double-blind Period | Participants With detectable CV (on study drug) | 7 Participants |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Participants With Detectable C-X-C Chemokine Receptor Type 4 (CXCR4)-Tropic Virus of the Double-blind Period | Participants With detectable CV anytime who discontinued | 3 Participants |
| Double-Blind Period - Placebo Plus an ART Regimen | Participants With Detectable C-X-C Chemokine Receptor Type 4 (CXCR4)-Tropic Virus of the Double-blind Period | Participants With detectable CV (on study drug) | 3 Participants |
| Double-Blind Period - Placebo Plus an ART Regimen | Participants With Detectable C-X-C Chemokine Receptor Type 4 (CXCR4)-Tropic Virus of the Double-blind Period | Participants With detectable CV anytime who discontinued | 2 Participants |
| Double-Blind Period - Placebo Plus an ART Regimen | Participants With Detectable C-X-C Chemokine Receptor Type 4 (CXCR4)-Tropic Virus of the Double-blind Period | Participants With detectable CV with other virologic failures | 2 Participants |
Secondary
Participants With Detectable CXCR4-Tropic Virus and Immune Decline (≥50% Fall in CD4 Count From Baseline) of the Double-blind Period
Viral tropism was determined using the Monogram Trofile assay and antiviral drug susceptibility was measured by Monogram PhenoSense GT assay, based on both genotypic and phenotypic sensitivity of HIV isolates. The lower limit of sensitivity of the Trofile assay employed in this study for detection of minor X-4 using variants was 5-10%. Participants with emergence of CXCR4 tropism who had a concomitant decline in CD4 count by ≥50% below baseline was also computed.
Time frame: Up to 48 weeks of the Double-blind Period
Population: The analysis population included all randomized participants who received at least 1 dose of study medication during the Double-blind Period. Participants enrolled in the Open Label Period were not included in this analysis population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Participants With Detectable CXCR4-Tropic Virus and Immune Decline (≥50% Fall in CD4 Count From Baseline) of the Double-blind Period | Participants with detectable CXCR4 virus pretreatment | 3 Participants |
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Participants With Detectable CXCR4-Tropic Virus and Immune Decline (≥50% Fall in CD4 Count From Baseline) of the Double-blind Period | Participants with ≥50% fall in CD4 count from baseline | 3 Participants |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Participants With Detectable CXCR4-Tropic Virus and Immune Decline (≥50% Fall in CD4 Count From Baseline) of the Double-blind Period | Participants with detectable CXCR4 virus pretreatment | 1 Participants |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Participants With Detectable CXCR4-Tropic Virus and Immune Decline (≥50% Fall in CD4 Count From Baseline) of the Double-blind Period | Participants with ≥50% fall in CD4 count from baseline | 1 Participants |
| Double-Blind Period - Placebo Plus an ART Regimen | Participants With Detectable CXCR4-Tropic Virus and Immune Decline (≥50% Fall in CD4 Count From Baseline) of the Double-blind Period | Participants with detectable CXCR4 virus pretreatment | 2 Participants |
| Double-Blind Period - Placebo Plus an ART Regimen | Participants With Detectable CXCR4-Tropic Virus and Immune Decline (≥50% Fall in CD4 Count From Baseline) of the Double-blind Period | Participants with ≥50% fall in CD4 count from baseline | 0 Participants |
Secondary
Participants With Detectable Vicriviroc Resistance of the Double-blind Period
Resistance testing was performed at Baseline and again at the time of virologic failure or study discontinuation using the Phenosense GT assay (Monogram Biosciences, South San Francisco, CA). This assay used a combination of genotypic and phenotypic resistance techniques to determine an overall sensitivity score (OSS). The OSS represents the total number of drugs in the optimized background regimen (OBT) to which the virus was fully susceptible. Partial sensitivity is not counted towards the OSS. VCV susceptibility testing was performed with a maximal percent inhibition (MPI) plateau value of \<85% as a cutoff for resistance.
Time frame: Up to 48 weeks of the Double-blind Period
Population: The analysis population included all randomized participants who received at least 1 dose of study medication during the Double-blind Period. Participants enrolled in the Open Label Period were not included in this analysis population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Participants With Detectable Vicriviroc Resistance of the Double-blind Period | 1 Participants |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Participants With Detectable Vicriviroc Resistance of the Double-blind Period | 4 Participants |
| Double-Blind Period - Placebo Plus an ART Regimen | Participants With Detectable Vicriviroc Resistance of the Double-blind Period | 0 Participants |
Secondary
Participants With HIV RNA <400 Copies/mL at Week 48 of the Double-blind Period
HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay. For participants who had HIV RNA below the lower quantification of the Standard assay (LOQ of 400 copies/mL), the AMPLICOR HIV-1.5 UltraSensitive assay was performed. If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. If the participants had no subsequent following value or discontinued study treatment before the time point of interest, then the change from baseline was set to zero.
Time frame: Week 48 of the Double-blind Period
Population: The analysis population included all randomized participants who received at least 1 dose of study medication during the Double-blind Period. Participants enrolled in the Open Label Period were not included in this analysis population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen | Participants With HIV RNA <400 Copies/mL at Week 48 of the Double-blind Period | 25 Participants |
| Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen | Participants With HIV RNA <400 Copies/mL at Week 48 of the Double-blind Period | 24 Participants |
| Double-Blind Period - Placebo Plus an ART Regimen | Participants With HIV RNA <400 Copies/mL at Week 48 of the Double-blind Period | 9 Participants |
p-value: 0.0007Cochran-Mantel-Haenszel
p-value: 0.0028Cochran-Mantel-Haenszel
Secondary
Time to Occurrence of an AIDS-defining Event of the Double-blind Period
All potential AIDS-defining events (ADEs) identified by investigators and the sponsor were submitted with supporting clinical data to an independent and blinded Adjudication Committee of HIV experts. To be analyzed as an ADE, the event required concurrence on the diagnosis by at least 2 of the 3 Adjudication Committee members. Their review included available clinical and laboratory data, including relevant radiologic, endoscopic, and pathology assessments, when applicable as well as autopsy reports and/or hospital admission and discharge summaries. An independent radiologist was called upon when necessary. Guidelines for Diagnosis of AIDS-Defining Conditions (CDC's 1993 Revised Classification System for HIV Infection and Expanded Surveillance Case Definition for AIDS Among Adolescents and Adults) was used.
Time frame: Up to 48 weeks of the Double-blind Period
Population: The analysis population included all randomized participants who received at least 1 dose of study medication and had an AIDS-defining Event during the Double-blind Period. Participants enrolled in the Open Label Period were not included in this analysis population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-Blind Period - Placebo Plus an ART Regimen | Time to Occurrence of an AIDS-defining Event of the Double-blind Period | 256 Days |