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Vicriviroc (SCH 417690) in Combination Treatment With Optimized ART Regimen in Experienced Participants (VICTOR-E1) (MK-7690-020/P03672)

Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT00243230
Collaborator
(none)
116
Enrollment
4
Arms
65.9
Actual Duration (Months)

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Vicriviroc 30 mg
  • Drug: Vicriviroc 20 mg
  • Drug: Placebo
  • Drug: Placebo
  • Drug: Background ART Regimen
 Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
116 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:
There were Double-blind and an Open Label extension period.
Primary Purpose:
Treatment
Official Title:
Vicriviroc (SCH 417690) in Combination Treatment With Optimized ART Regimen in Experienced Subjects (VICTOR-E1)
Actual Study Start Date :
Sep 19, 2005
Actual Primary Completion Date :
Oct 19, 2007
Actual Study Completion Date :
Mar 17, 2011

Arms and Interventions

Arm Intervention/Treatment
Experimental: Double-Blind - Vicriviroc 30 mg

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.

Drug: Vicriviroc 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).
Other Names:
  • SCH 417690

    • Drug: Background 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.
    Experimental: Double-Blind - Vicriviroc 20 mg

    Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.

    Drug: Vicriviroc 20 mg
    Two tablets of vicriviroc 10 mg once daily for 48 weeks.
    Other Names:
  • SCH 417690

    • Drug: Placebo
    Two tablets of placebo once daily for 48 weeks.

    Drug: Background 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.
    Placebo Comparator: Double-Blind - Placebo

    Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.

    Drug: Placebo
    Three tablets of placebo once daily for 48 weeks.

    Drug: Background 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.
    Experimental: Open-label - Vicriviroc 30 mg

    Vicriviroc 30 mg once daily (QD), orally (PO), plus an open-label optimized ART regimen containing a ritonavir-boosted protease inhibitor (PI/r) for up to 45 months.

    Drug: Vicriviroc 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).
    Other Names:
  • SCH 417690

    • Drug: Background 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.

    Outcome Measures

    Primary Outcome Measures

    1. 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 Outcome Measures

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    6. 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.

    7. 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.

    8. 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.

    9. 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.

    10. 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.

    11. 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.

    12. 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.

    13. 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.

    14. 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.

    15. 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.

    16. 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.

    17. 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.

    18. 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.

    19. 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.

    20. 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.

    21. 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.

    22. 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.

    23. 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%.

    24. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Merck Sharp & Dohme LLC

    Investigators

    • Study Director: Medical Director, Merck Sharp & Dohme LLC

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT00243230
    Other Study ID Numbers:
    • P03672
    • 2005-001057-21
    • MK-7690-020
    • P03672
    First Posted:
    Oct 21, 2005
    Last Update Posted:
    Jun 8, 2021
    Last Verified:
    May 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    HIV Infections

    Study Results

    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.
    Pre-assignment Detail
    Arm/Group Title 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 Open-Label Period - Vicriviroc 30 mg Plus an ART Regimen
    Arm/Group Description 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. Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Vicriviroc 30 mg once daily (QD), orally (PO), plus an open-label optimized ART regimen containing a ritonavir-boosted protease inhibitor (PI/r) for up to 45 months.
    Period Title: Double-Blind Period
    STARTED 39 40 37 0
    Treated 39 40 35 0
    COMPLETED 33 35 18 0
    NOT COMPLETED 6 5 19 0
    Period Title: Double-Blind Period
    STARTED 0 0 0 85
    COMPLETED 0 0 0 0
    NOT COMPLETED 0 0 0 85

    Baseline Characteristics

    Arm/Group Title 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
    Arm/Group Description 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. Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Total of all reporting groups
    Overall Participants 39 40 37 116
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    44.9
    (7.3)
    44.0
    (8.0)
    45.5
    (8.8)
    44.8
    (8.0)
    Sex: Female, Male (Count of Participants)
    Female
    6
    15.4%
    9
    22.5%
    11
    29.7%
    26
    22.4%
    Male
    33
    84.6%
    31
    77.5%
    26
    70.3%
    90
    77.6%
    Race/Ethnicity, Customized (Count of Participants)
    White
    26
    66.7%
    32
    80%
    21
    56.8%
    79
    68.1%
    Black
    9
    23.1%
    3
    7.5%
    8
    21.6%
    20
    17.2%
    Asian
    0
    0%
    1
    2.5%
    0
    0%
    1
    0.9%
    Other
    4
    10.3%
    4
    10%
    8
    21.6%
    16
    13.8%

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in Log10 Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) at Week 48 of the Double-blind Period
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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
    Arm/Group Description 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. Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.
    Measure Participants 39 40 35
    Log10 HIV RNA at Baseline.
    4.52
    (0.88)
    4.50
    (0.89)
    4.62
    (0.79)
    Change from Baseline in Log10 HIV RNA at Week 48.
    -1.78
    (1.31)
    -1.73
    (1.31)
    -0.80
    (1.31)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen, Double-Blind Period - Placebo Plus an ART Regimen
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0017
    Comments
    Method ANOVA
    Comments ANOVA model adjusted for treatment and stratification factors - the use of T20 in current OBT and the baseline HIV-1 RNA ≤100,000 copies/mL.
    Method of Estimation Estimation Parameter VCV 30 mg vs. Placebo
    Estimated Value -0.98
    Confidence Interval (2-Sided) 95%
    -1.58 to -0.37
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen, Double-Blind Period - Placebo Plus an ART Regimen
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0026
    Comments
    Method ANOVA
    Comments ANOVA model adjusted for treatment and stratification factors - the use of T20 in current OBT and the baseline HIV-1 RNA ≤100,000 copies/mL.
    Method of Estimation Estimation Parameter VCV 20 mg vs. Placebo
    Estimated Value -0.93
    Confidence Interval () 95%
    -1.54 to -0.33
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Participants With ≥1.0 log10 Change From Baseline HIV RNA at Week 48 of the Double-blind Period
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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
    Arm/Group Description 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. Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.
    Measure Participants 39 40 35
    Count of Participants [Participants]
    26
    66.7%
    25
    62.5%
    12
    32.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen, Double-Blind Period - Placebo Plus an ART Regimen
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0052
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel Haenszel Test adjusted for stratification factors of T20 use in current OBT and baseline HIV-1 RNA.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen, Double-Blind Period - Placebo Plus an ART Regimen
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0190
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel Haenszel Test adjusted for stratification factors of T20 use in current OBT and baseline HIV-1 RNA.
    3. Secondary Outcome
    Title Participants With HIV RNA <400 Copies/mL at Week 48 of the Double-blind Period
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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
    Arm/Group Description 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. Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.
    Measure Participants 39 40 35
    Count of Participants [Participants]
    25
    64.1%
    24
    60%
    9
    24.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen, Double-Blind Period - Placebo Plus an ART Regimen
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0007
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel Haenszel Test adjusted for stratification factors of T20 use in current OBT and baseline HIV-1 RNA.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen, Double-Blind Period - Placebo Plus an ART Regimen
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0028
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel Haenszel Test adjusted for stratification factors of T20 use in current OBT and baseline HIV-1 RNA.
    4. Secondary Outcome
    Title Participants With a Time to Loss of Virologic Response (TLOVR) Based on 0.5 Log10 Reduction by 48 Weeks of the Double-blind Period
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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
    Arm/Group Description 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. Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.
    Measure Participants 39 40 35
    Participants with Sustained ≥0.5 Log10 Reduction by Week 4
    31
    79.5%
    32
    80%
    15
    40.5%
    Participants with Rebound by Week 12
    1
    2.6%
    1
    2.5%
    1
    2.7%
    Participants with Rebound by Week 24
    2
    5.1%
    1
    2.5%
    1
    2.7%
    Participants with Rebound after Week 24
    1
    2.6%
    1
    2.5%
    1
    2.7%
    Participants Suppressed through Week 48
    27
    69.2%
    29
    72.5%
    12
    32.4%
    Participants with No ≥0.5 Log10 Reduction by Week 4
    1
    2.6%
    2
    5%
    3
    8.1%
    5. Secondary Outcome
    Title Change From Baseline in Log10 HIV RNA at Week 12 of the Double-blind Period
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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
    Arm/Group Description 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. Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.
    Measure Participants 39 40 35
    Log10 HIV RNA at Baseline.
    4.52
    (0.88)
    4.50
    (0.89)
    4.62
    (0.79)
    Change from Baseline in Log10 HIV RNA at Week 12.
    -2.11
    (1.14)
    -1.94
    (1.14)
    -1.11
    (1.14)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen, Double-Blind Period - Placebo Plus an ART Regimen
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0002
    Comments
    Method ANOVA
    Comments ANOVA model adjusted for treatment and stratification factors - the use of T20 in current OBT and the baseline HIV-1 RNA ≤100,000 copies/mL.
    Method of Estimation Estimation Parameter Vicriviroc 30mg - Placebo
    Estimated Value -1.00
    Confidence Interval (2-Sided) 95%
    -1.53 to -0.48
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen, Double-Blind Period - Placebo Plus an ART Regimen
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0020
    Comments
    Method ANOVA
    Comments ANOVA model adjusted for treatment and stratification factors - the use of T20 in current OBT and the baseline HIV-1 RNA ≤100,000 copies/mL.
    Method of Estimation Estimation Parameter Vicriviroc 20 mg - Placebo
    Estimated Value -0.84
    Confidence Interval (2-Sided) 95%
    -1.36 to -0.31
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Change From Baseline in Log10 HIV RNA at Week 24 of the Double-blind Period
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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
    Arm/Group Description 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. Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.
    Measure Participants 39 40 35
    Log10 HIV RNA at Baseline.
    4.52
    (0.88)
    4.50
    (0.89)
    4.62
    (0.79)
    Change from Baseline in Log10 HIV RNA at Week 24.
    -2.07
    (1.28)
    -2.04
    (1.28)
    -0.96
    (1.28)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen, Double-Blind Period - Placebo Plus an ART Regimen
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0003
    Comments
    Method ANOVA
    Comments ANOVA model adjusted for treatment and stratification factors - the use of T20 in current OBT and the baseline HIV-1 RNA <=100,000 copies/mL.
    Method of Estimation Estimation Parameter Vicriviroc 30 mg - Placebo
    Estimated Value -1.10
    Confidence Interval (2-Sided) 95%
    -1.69 to -0.51
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen, Double-Blind Period - Placebo Plus an ART Regimen
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0004
    Comments
    Method ANOVA
    Comments ANOVA model adjusted for treatment and stratification factors - the use of T20 in current OBT and the baseline HIV-1 RNA <=100,000 copies/mL.
    Method of Estimation Estimation Parameter Vicriviroc 20 mg - Placebo
    Estimated Value -1.07
    Confidence Interval (2-Sided) 95%
    -1.66 to -0.49
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Change From Baseline CD4 Cells Count at Week 12 of the Double-blind Period
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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
    Arm/Group Description 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. Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.
    Measure Participants 39 39 35
    CD4 Cells Count at Baseline
    202.23
    (159.22)
    202.10
    (144.47)
    214.41
    (185.62)
    Change from Baseline CD4 Cells Count at Week 12
    109.85
    (110.23)
    94.46
    (110.31)
    52.09
    (110.21)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen, Double-Blind Period - Placebo Plus an ART Regimen
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0264
    Comments
    Method ANOVA
    Comments ANOVA model adjusted for treatment and stratification factors - the use of T20 in current OBT and the baseline HIV-1 RNA ≤100,000 copies/mL.
    Method of Estimation Estimation Parameter VCV 30 mg - Placebo
    Estimated Value 57.76
    Confidence Interval (2-Sided) 95%
    6.90 to 108.61
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen, Double-Blind Period - Placebo Plus an ART Regimen
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1020
    Comments
    Method ANOVA
    Comments ANOVA model adjusted for treatment and stratification factors - the use of T20 in current OBT and the baseline HIV-1 RNA ≤100,000 copies/mL.
    Method of Estimation Estimation Parameter VCV 20 mg - Placebo
    Estimated Value 42.36
    Confidence Interval (2-Sided) 95%
    -8.55 to 93.28
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Change From Baseline CD4 Count at Week 24 of the Double-blind Period
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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
    Arm/Group Description 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. Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.
    Measure Participants 39 39 35
    CD4 Count at Baseline.
    202.23
    (159.22)
    202.10
    (144.47)
    214.41
    (185.62)
    Change from Baseline CD4 Count at Week 24.
    97.58
    (113.66)
    103.58
    (113.74)
    59.46
    (113.64)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen, Double-Blind Period - Placebo Plus an ART Regimen
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1525
    Comments
    Method ANOVA
    Comments ANOVA model adjusted for treatment and stratification factors - the use of T20 in current OBT and the baseline HIV-1 RNA ≤100,000 copies/mL.
    Method of Estimation Estimation Parameter VCV 30 mg - Placebo
    Estimated Value 38.12
    Confidence Interval (2-Sided) 95%
    -14.32 to 90.56
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen, Double-Blind Period - Placebo Plus an ART Regimen
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0987
    Comments
    Method ANOVA
    Comments ANOVA model adjusted for treatment and stratification factors - the use of T20 in current OBT and the baseline HIV-1 RNA ≤100,000 copies/mL.
    Method of Estimation Estimation Parameter VCV 20 mg - Placebo
    Estimated Value 44.12
    Confidence Interval (2-Sided) 95%
    -8.38 to 96.61
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title Change From Baseline CD4 Count at Week 48 of the Double-blind Period
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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
    Arm/Group Description 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. Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.
    Measure Participants 39 39 35
    CD4 Count at Baseline.
    202.23
    (159.22)
    202.10
    (144.47)
    214.41
    (185.62)
    Change from Baseline CD4 Count at Week 48.
    102.12
    (141.68)
    133.88
    (141.79)
    64.80
    (141.65)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen, Double-Blind Period - Placebo Plus an ART Regimen
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2603
    Comments
    Method ANOVA
    Comments ANOVA model adjusted for treatment and stratification factors - the use of T20 in current OBT and the baseline HIV-1 RNA ≤100,000 copies/mL.
    Method of Estimation Estimation Parameter VCV 30 mg - Placebo
    Estimated Value 37.32
    Confidence Interval (2-Sided) 95%
    -28.05 to 102.68
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen, Double-Blind Period - Placebo Plus an ART Regimen
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0387
    Comments
    Method ANOVA
    Comments ANOVA model adjusted for treatment and stratification factors - the use of T20 in current OBT and the baseline HIV-1 RNA ≤100,000 copies/mL.
    Method of Estimation Estimation Parameter VCV 20 mg - Placebo
    Estimated Value 69.08
    Confidence Interval (2-Sided) 95%
    3.64 to 134.52
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    10. Secondary Outcome
    Title Change From Baseline CD4 Count at Month 42 of the Open Label Extension
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Open-Label Period - Vicriviroc 30 mg Plus an ART Regimen
    Arm/Group Description Vicriviroc 30 mg once daily (QD), orally (PO), plus an open-label optimized ART regimen containing a ritonavir-boosted protease inhibitor (PI/r) for up to 45 months.
    Measure Participants 85
    CD4 Count at Baseline (Open Label Extension).
    366.16
    (191.86)
    Change from Baseline CD4 Count at Month 42.
    -78.67
    (283.28)
    11. Secondary Outcome
    Title Participants With <400 Copies/mL HIV RNA at Week 12 of the Double-blind Period
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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
    Arm/Group Description 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. Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.
    Measure Participants 39 40 35
    Count of Participants [Participants]
    28
    71.8%
    25
    62.5%
    14
    37.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen, Double-Blind Period - Placebo Plus an ART Regimen
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0031
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel Haenszel Test adjusted for stratification factors of T20 use in current OBT and baseline HIV-1 RNA.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen, Double-Blind Period - Placebo Plus an ART Regimen
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0480
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel Haenszel Test adjusted for stratification factors of T20 use in current OBT and baseline HIV-1 RNA.
    12. Secondary Outcome
    Title Participants With <400 Copies/mL HIV RNA at Week 24 of the Double-blind Period
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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
    Arm/Group Description 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. Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.
    Measure Participants 39 40 35
    Count of Participants [Participants]
    28
    71.8%
    29
    72.5%
    12
    32.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen, Double-Blind Period - Placebo Plus an ART Regimen
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0009
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel Haenszel Test adjusted for stratification factors of T20 use in current OBT and baseline HIV-1 RNA.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen, Double-Blind Period - Placebo Plus an ART Regimen
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0009
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel Haenszel Test adjusted for stratification factors of T20 use in current OBT and baseline HIV-1 RNA.
    13. Secondary Outcome
    Title Number of Participants With <50, 50 to <400, and ≥400 Copies/mL HIV RNA of the Open Label Extension
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Open-Label Period - Vicriviroc 30 mg Plus an ART Regimen
    Arm/Group Description Vicriviroc 30 mg once daily (QD), orally (PO), plus an open-label optimized ART regimen containing a ritonavir-boosted protease inhibitor (PI/r) for up to 45 months.
    Measure Participants 85
    Group 1. Baseline for RNA <50 copies/mL
    48
    123.1%
    Group 1. Last RNA <50 copies/mL
    42
    107.7%
    Group 1. Last RNA 50 to <400 copies/mL
    5
    12.8%
    Group 1. Last RNA ≥400 copies/mL
    1
    2.6%
    Group 2. Baseline for RNA 50 to <400 copies/mL
    10
    25.6%
    Group 2. Last RNA <50 copies/mL
    5
    12.8%
    Group 2. Last RNA 50 to <400 copies/mL
    2
    5.1%
    Group 2. Last RNA ≥400 copies/mL
    3
    7.7%
    Group 3. Baseline for RNA ≥400 copies/mL
    27
    69.2%
    Group 3. Last RNA <50 copies/mL
    10
    25.6%
    Group 3. Last RNA 50 to <400 copies/mL
    0
    0%
    Group 3. Last RNA ≥400 copies/mL
    15
    38.5%
    14. Secondary Outcome
    Title Participants With <50 Copies/mL HIV RNA at Week 12 of the Double-blind Period
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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
    Arm/Group Description 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. Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.
    Measure Participants 39 40 35
    Count of Participants [Participants]
    18
    46.2%
    17
    42.5%
    8
    21.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen, Double-Blind Period - Placebo Plus an ART Regimen
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0225
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel Haenszel Test adjusted for stratification factors of T20 use in current OBT and baseline HIV-1 RNA.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen, Double-Blind Period - Placebo Plus an ART Regimen
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0582
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel Haenszel Test adjusted for stratification factors of T20 use in current OBT and baseline HIV-1 RNA.
    15. Secondary Outcome
    Title Participants With <50 Copies/mL HIV RNA at Week 24 of the Double-blind Period
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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
    Arm/Group Description 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. Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.
    Measure Participants 39 40 35
    Count of Participants [Participants]
    25
    64.1%
    23
    57.5%
    9
    24.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen, Double-Blind Period - Placebo Plus an ART Regimen
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0009
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel Haenszel Test adjusted for stratification factors of T20 use in current OBT and baseline HIV-1 RNA.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen, Double-Blind Period - Placebo Plus an ART Regimen
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0038
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel Haenszel Test adjusted for stratification factors of T20 use in current OBT and baseline HIV-1 RNA.
    16. Secondary Outcome
    Title Participants With <50 Copies/mL HIV RNA at Week 48 of the Double-blind Period
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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
    Arm/Group Description 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. Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.
    Measure Participants 39 40 35
    Count of Participants [Participants]
    22
    56.4%
    21
    52.5%
    5
    13.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen, Double-Blind Period - Placebo Plus an ART Regimen
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0002
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel Haenszel Test adjusted for stratification factors of T20 use in current OBT and baseline HIV-1 RNA.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen, Double-Blind Period - Placebo Plus an ART Regimen
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0004
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel Haenszel Test adjusted for stratification factors of T20 use in current OBT and baseline HIV-1 RNA.
    17. Secondary Outcome
    Title Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Events of the Double-blind Period
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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
    Arm/Group Description 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. Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.
    Measure Participants 39 40 35
    Count of Participants [Participants]
    0
    0%
    0
    0%
    1
    2.7%
    18. Secondary Outcome
    Title Participants With AIDS-defining Events of the Open Label Extension
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Open-Label Period - Vicriviroc 30 mg Plus an ART Regimen
    Arm/Group Description Vicriviroc 30 mg once daily (QD), orally (PO), plus an open-label optimized ART regimen containing a ritonavir-boosted protease inhibitor (PI/r) for up to 45 months.
    Measure Participants 85
    Count of Participants [Participants]
    1
    2.6%
    19. Secondary Outcome
    Title Time to Occurrence of an AIDS-defining Event of the Double-blind Period
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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
    Arm/Group Description 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. Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.
    Measure Participants 0 0 1
    Number [Days]
    256
    20. Secondary Outcome
    Title Observed Minimum Serum Concentration of Vicriviroc (Cmin) of the Double-blind Period
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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
    Arm/Group Description 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. Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.
    Measure Participants 39 40 0
    Mean (Standard Deviation) [ng/mL]
    206.56
    (76.82)
    156.95
    (62.17)
    21. Secondary Outcome
    Title Observed Maximum (Peak) Plasma Concentration of Vicriviroc (Cmax) of the Double-blind Period
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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
    Arm/Group Description 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. Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.
    Measure Participants 39 40 0
    Mean (Standard Deviation) [ng/mL]
    316.21
    (84.41)
    229.33
    (61.74)
    22. Secondary Outcome
    Title Area Under the Plasma Concentration Versus Time Curve of Vicriviroc (AUC) of the Double-blind Period
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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
    Arm/Group Description 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. Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.
    Measure Participants 39 40 0
    Mean (Standard Deviation) [hr*ng/mL]
    5795.62
    (1906.59)
    4314.88
    (1497.70)
    23. Secondary Outcome
    Title Participants With Detectable Vicriviroc Resistance of the Double-blind Period
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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
    Arm/Group Description 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. Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.
    Measure Participants 39 40 35
    Count of Participants [Participants]
    1
    2.6%
    4
    10%
    0
    0%
    24. Secondary Outcome
    Title Participants With Detectable C-X-C Chemokine Receptor Type 4 (CXCR4)-Tropic Virus of the Double-blind Period
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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
    Arm/Group Description 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. Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.
    Measure Participants 39 40 35
    Participants With detectable CV (on study drug)
    9
    23.1%
    7
    17.5%
    3
    8.1%
    Participants With detectable CV with other virologic failures
    8
    20.5%
    7
    17.5%
    2
    5.4%
    Participants With detectable CV anytime who discontinued
    4
    10.3%
    3
    7.5%
    2
    5.4%
    25. Secondary Outcome
    Title Participants With Detectable CXCR4-Tropic Virus and Immune Decline (≥50% Fall in CD4 Count From Baseline) of the Double-blind Period
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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
    Arm/Group Description 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. Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks.
    Measure Participants 39 40 35
    Participants with detectable CXCR4 virus pretreatment
    3
    7.7%
    1
    2.5%
    2
    5.4%
    Participants with ≥50% fall in CD4 count from baseline
    3
    7.7%
    1
    2.5%
    0
    0%

    Adverse Events

    Time Frame Up to 48 weeks for the Double-blind Period Up to 45 months for the Open Label Period.
    Adverse Event Reporting Description The analysis population for adverse events included all randomized participants who received at least one dose of study drug during the Double-Blind Treatment Period and during the Open Label Extension. The analysis population for All-Cause Mortality was the all randomized population. MedDRA Version 10.1 was used for analysis of the Double-Blind Treatment Period data, and Version 13.1 was used for analysis of the Open Label Extension data.
    Arm/Group Title 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 Open-Label Period - Vicriviroc 30 mg Plus an ART Regimen
    Arm/Group Description 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. Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Vicriviroc 30 mg once daily (QD), orally (PO), plus an open-label optimized ART regimen containing a ritonavir-boosted protease inhibitor (PI/r) for up to 45 months.
    All Cause Mortality
    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 Open-Label Period - Vicriviroc 30 mg Plus an ART Regimen
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/39 (0%) 2/40 (5%) 2/37 (5.4%) 1/85 (1.2%)
    Serious Adverse Events
    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 Open-Label Period - Vicriviroc 30 mg Plus an ART Regimen
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/39 (10.3%) 5/40 (12.5%) 5/35 (14.3%) 13/85 (15.3%)
    Blood and lymphatic system disorders
    ANAEMIA 0/39 (0%) 0 0/40 (0%) 0 2/35 (5.7%) 2 0/85 (0%) 0
    COAGULOPATHY 0/39 (0%) 0 1/40 (2.5%) 1 0/35 (0%) 0 0/85 (0%) 0
    LYMPHADENOPATHY 0/39 (0%) 0 1/40 (2.5%) 1 0/35 (0%) 0 1/85 (1.2%) 1
    RETROPERITONEAL LYMPHADENOPATHY 0/39 (0%) 0 0/40 (0%) 0 0/35 (0%) 0 1/85 (1.2%) 1
    Cardiac disorders
    ACUTE CORONARY SYNDROME 0/39 (0%) 0 1/40 (2.5%) 1 0/35 (0%) 0 0/85 (0%) 0
    CARDIOPULMONARY FAILURE 0/39 (0%) 0 0/40 (0%) 0 1/35 (2.9%) 1 0/85 (0%) 0
    PERICARDITIS URAEMIC 1/39 (2.6%) 1 0/40 (0%) 0 0/35 (0%) 0 0/85 (0%) 0
    Congenital, familial and genetic disorders
    DYSPLASTIC NAEVUS SYNDROME 0/39 (0%) 0 0/40 (0%) 0 0/35 (0%) 0 1/85 (1.2%) 1
    Gastrointestinal disorders
    ABDOMINAL PAIN 0/39 (0%) 0 1/40 (2.5%) 1 0/35 (0%) 0 0/85 (0%) 0
    ASCITES 0/39 (0%) 0 1/40 (2.5%) 1 0/35 (0%) 0 0/85 (0%) 0
    DIARRHOEA 0/39 (0%) 0 0/40 (0%) 0 1/35 (2.9%) 1 0/85 (0%) 0
    LARGE INTESTINAL ULCER 1/39 (2.6%) 1 0/40 (0%) 0 0/35 (0%) 0 0/85 (0%) 0
    INGUINAL HERNIA 0/39 (0%) 0 0/40 (0%) 0 0/35 (0%) 0 1/85 (1.2%) 1
    General disorders
    CHEST PAIN 0/39 (0%) 0 0/40 (0%) 0 1/35 (2.9%) 1 1/85 (1.2%) 1
    MULTI-ORGAN FAILURE 0/39 (0%) 0 1/40 (2.5%) 1 0/35 (0%) 0 0/85 (0%) 0
    PYREXIA 1/39 (2.6%) 1 0/40 (0%) 0 0/35 (0%) 0 0/85 (0%) 0
    Hepatobiliary disorders
    CHOLESTASIS 0/39 (0%) 0 1/40 (2.5%) 1 0/35 (0%) 0 0/85 (0%) 0
    JAUNDICE 0/39 (0%) 0 1/40 (2.5%) 1 0/35 (0%) 0 0/85 (0%) 0
    Infections and infestations
    GASTROENTERITIS ESCHERICHIA COLI 0/39 (0%) 0 0/40 (0%) 0 1/35 (2.9%) 1 0/85 (0%) 0
    GASTROINTESTINAL INFECTION 0/39 (0%) 0 0/40 (0%) 0 1/35 (2.9%) 1 0/85 (0%) 0
    LOCALISED INFECTION 0/39 (0%) 0 0/40 (0%) 0 1/35 (2.9%) 1 0/85 (0%) 0
    PNEUMONIA 1/39 (2.6%) 1 0/40 (0%) 0 0/35 (0%) 0 0/85 (0%) 0
    PNEUMONIA PRIMARY ATYPICAL 0/39 (0%) 0 1/40 (2.5%) 1 0/35 (0%) 0 0/85 (0%) 0
    SEPSIS 0/39 (0%) 0 1/40 (2.5%) 1 0/35 (0%) 0 0/85 (0%) 0
    UPPER RESPIRATORY TRACT INFECTION 0/39 (0%) 0 0/40 (0%) 0 1/35 (2.9%) 1 0/85 (0%) 0
    UROSEPSIS 0/39 (0%) 0 0/40 (0%) 0 1/35 (2.9%) 1 0/85 (0%) 0
    URINARY TRACT INFECTION 0/39 (0%) 0 0/40 (0%) 0 0/35 (0%) 0 1/85 (1.2%) 1
    Injury, poisoning and procedural complications
    FALL 0/39 (0%) 0 0/40 (0%) 0 0/35 (0%) 0 1/85 (1.2%) 1
    FEMUR FRACTURE 0/39 (0%) 0 0/40 (0%) 0 0/35 (0%) 0 2/85 (2.4%) 2
    SKIN LACERATION 0/39 (0%) 0 0/40 (0%) 0 0/35 (0%) 0 1/85 (1.2%) 1
    SUBDURAL HAEMATOMA 0/39 (0%) 0 0/40 (0%) 0 0/35 (0%) 0 1/85 (1.2%) 1
    Investigations
    BLOOD CREATINE INCREASED 1/39 (2.6%) 1 0/40 (0%) 0 0/35 (0%) 0 0/85 (0%) 0
    BLOOD CREATININE INCREASED 1/39 (2.6%) 1 0/40 (0%) 0 0/35 (0%) 0 0/85 (0%) 0
    Metabolism and nutrition disorders
    DEHYDRATION 2/39 (5.1%) 2 0/40 (0%) 0 0/35 (0%) 0 0/85 (0%) 0
    HYPOKALAEMIA 0/39 (0%) 0 0/40 (0%) 0 1/35 (2.9%) 1 0/85 (0%) 0
    METABOLIC ACIDOSIS 1/39 (2.6%) 1 0/40 (0%) 0 0/35 (0%) 0 0/85 (0%) 0
    Musculoskeletal and connective tissue disorders
    OSTEONECROSIS 0/39 (0%) 0 0/40 (0%) 0 0/35 (0%) 0 1/85 (1.2%) 1
    PAIN IN EXTREMITY 0/39 (0%) 0 0/40 (0%) 0 0/35 (0%) 0 1/85 (1.2%) 1
    RHABDOMYOLYSIS 0/39 (0%) 0 0/40 (0%) 0 0/35 (0%) 0 1/85 (1.2%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    ANAL CANCER 0/39 (0%) 0 0/40 (0%) 0 0/35 (0%) 0 1/85 (1.2%) 1
    BASAL CELL CARCINOMA 0/39 (0%) 0 0/40 (0%) 0 0/35 (0%) 0 1/85 (1.2%) 1
    HODGKIN'S DISEASE 0/39 (0%) 0 0/40 (0%) 0 0/35 (0%) 0 1/85 (1.2%) 1
    PENIS CARCINOMA RECURRENT 0/39 (0%) 0 0/40 (0%) 0 0/35 (0%) 0 1/85 (1.2%) 1
    Nervous system disorders
    CONVULSION 0/39 (0%) 0 0/40 (0%) 0 1/35 (2.9%) 1 0/85 (0%) 0
    DEPRESSED LEVEL OF CONSCIOUSNESS 0/39 (0%) 0 0/40 (0%) 0 1/35 (2.9%) 1 0/85 (0%) 0
    DIZZINESS 1/39 (2.6%) 1 0/40 (0%) 0 0/35 (0%) 0 0/85 (0%) 0
    LACUNAR INFARCTION 0/39 (0%) 0 1/40 (2.5%) 1 0/35 (0%) 0 0/85 (0%) 0
    DYSKINESIA 0/39 (0%) 0 0/40 (0%) 0 0/35 (0%) 0 1/85 (1.2%) 1
    TRANSIENT ISCHAEMIC ATTACK 0/39 (0%) 0 0/40 (0%) 0 0/35 (0%) 0 1/85 (1.2%) 1
    Renal and urinary disorders
    CALCULUS URINARY 0/39 (0%) 0 0/40 (0%) 0 1/35 (2.9%) 1 0/85 (0%) 0
    HYDRONEPHROSIS 0/39 (0%) 0 0/40 (0%) 0 1/35 (2.9%) 1 0/85 (0%) 0
    RENAL FAILURE ACUTE 1/39 (2.6%) 1 0/40 (0%) 0 0/35 (0%) 0 0/85 (0%) 0
    URETERIC OBSTRUCTION 0/39 (0%) 0 0/40 (0%) 0 1/35 (2.9%) 1 0/85 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    COUGH 1/39 (2.6%) 1 0/40 (0%) 0 0/35 (0%) 0 0/85 (0%) 0
    LUNG DISORDER 0/39 (0%) 0 1/40 (2.5%) 1 0/35 (0%) 0 0/85 (0%) 0
    PLEURAL EFFUSION 0/39 (0%) 0 1/40 (2.5%) 1 0/35 (0%) 0 0/85 (0%) 0
    Surgical and medical procedures
    HYSTERECTOMY 0/39 (0%) 0 0/40 (0%) 0 0/35 (0%) 0 1/85 (1.2%) 1
    SALPINGO-OOPHORECTOMY BILATERAL 0/39 (0%) 0 0/40 (0%) 0 0/35 (0%) 0 1/85 (1.2%) 1
    SPINAL FUSION SURGERY 0/39 (0%) 0 0/40 (0%) 0 0/35 (0%) 0 1/85 (1.2%) 1
    Vascular disorders
    DEEP VEIN THROMBOSIS 0/39 (0%) 0 1/40 (2.5%) 1 0/35 (0%) 0 0/85 (0%) 0
    HYPERTENSION 1/39 (2.6%) 1 0/40 (0%) 0 0/35 (0%) 0 0/85 (0%) 0
    ORTHOSTATIC HYPOTENSION 0/39 (0%) 0 0/40 (0%) 0 0/35 (0%) 0 1/85 (1.2%) 1
    Other (Not Including Serious) Adverse Events
    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 Open-Label Period - Vicriviroc 30 mg Plus an ART Regimen
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 34/39 (87.2%) 31/40 (77.5%) 29/35 (82.9%) 58/85 (68.2%)
    Blood and lymphatic system disorders
    ANAEMIA 1/39 (2.6%) 1 0/40 (0%) 0 3/35 (8.6%) 3 1/85 (1.2%) 1
    LYMPHADENOPATHY 3/39 (7.7%) 5 6/40 (15%) 6 2/35 (5.7%) 2 0/85 (0%) 0
    NEUTROPENIA 1/39 (2.6%) 2 0/40 (0%) 0 2/35 (5.7%) 3 0/85 (0%) 0
    Gastrointestinal disorders
    ABDOMINAL PAIN 0/39 (0%) 0 3/40 (7.5%) 3 0/35 (0%) 0 2/85 (2.4%) 2
    ABDOMINAL PAIN UPPER 1/39 (2.6%) 1 5/40 (12.5%) 5 0/35 (0%) 0 0/85 (0%) 0
    DIARRHOEA 15/39 (38.5%) 17 11/40 (27.5%) 17 9/35 (25.7%) 13 9/85 (10.6%) 10
    DYSPEPSIA 1/39 (2.6%) 1 2/40 (5%) 2 2/35 (5.7%) 2 3/85 (3.5%) 3
    FLATULENCE 1/39 (2.6%) 1 2/40 (5%) 2 4/35 (11.4%) 4 1/85 (1.2%) 1
    NAUSEA 5/39 (12.8%) 5 3/40 (7.5%) 5 5/35 (14.3%) 7 2/85 (2.4%) 2
    VOMITING 2/39 (5.1%) 2 2/40 (5%) 2 3/35 (8.6%) 3 0/85 (0%) 0
    General disorders
    ASTHENIA 2/39 (5.1%) 2 1/40 (2.5%) 1 3/35 (8.6%) 3 1/85 (1.2%) 2
    FATIGUE 2/39 (5.1%) 2 5/40 (12.5%) 6 3/35 (8.6%) 3 3/85 (3.5%) 3
    OEDEMA PERIPHERAL 0/39 (0%) 0 0/40 (0%) 0 2/35 (5.7%) 4 3/85 (3.5%) 3
    PYREXIA 4/39 (10.3%) 4 4/40 (10%) 8 4/35 (11.4%) 5 6/85 (7.1%) 9
    Hepatobiliary disorders
    HYPERBILIRUBINAEMIA 1/39 (2.6%) 1 0/40 (0%) 0 2/35 (5.7%) 2 0/85 (0%) 0
    Infections and infestations
    BRONCHITIS 3/39 (7.7%) 3 0/40 (0%) 0 2/35 (5.7%) 2 6/85 (7.1%) 10
    FOLLICULITIS 2/39 (5.1%) 2 0/40 (0%) 0 1/35 (2.9%) 1 1/85 (1.2%) 1
    GASTROENTERITIS VIRAL 2/39 (5.1%) 2 0/40 (0%) 0 0/35 (0%) 0 0/85 (0%) 0
    INFLUENZA 3/39 (7.7%) 3 5/40 (12.5%) 5 1/35 (2.9%) 1 8/85 (9.4%) 11
    NASOPHARYNGITIS 1/39 (2.6%) 1 0/40 (0%) 0 2/35 (5.7%) 2 3/85 (3.5%) 4
    ONYCHOMYCOSIS 3/39 (7.7%) 3 3/40 (7.5%) 3 1/35 (2.9%) 1 1/85 (1.2%) 2
    ORAL CANDIDIASIS 2/39 (5.1%) 3 0/40 (0%) 0 0/35 (0%) 0 1/85 (1.2%) 2
    SINUSITIS 2/39 (5.1%) 2 4/40 (10%) 5 2/35 (5.7%) 2 10/85 (11.8%) 12
    TINEA PEDIS 4/39 (10.3%) 4 0/40 (0%) 0 1/35 (2.9%) 1 1/85 (1.2%) 1
    UPPER RESPIRATORY TRACT INFECTION 2/39 (5.1%) 2 2/40 (5%) 2 0/35 (0%) 0 11/85 (12.9%) 15
    PNEUMONIA 0/39 (0%) 0 1/40 (2.5%) 2 1/35 (2.9%) 1 5/85 (5.9%) 6
    URINARY TRACT INFECTION 0/39 (0%) 0 1/40 (2.5%) 1 1/35 (2.9%) 1 6/85 (7.1%) 8
    Investigations
    BLOOD CREATINE PHOSPHOKINASE INCREASED 2/39 (5.1%) 2 1/40 (2.5%) 1 1/35 (2.9%) 1 1/85 (1.2%) 1
    LIPASE INCREASED 3/39 (7.7%) 5 0/40 (0%) 0 2/35 (5.7%) 3 1/85 (1.2%) 1
    WEIGHT DECREASED 2/39 (5.1%) 2 0/40 (0%) 0 1/35 (2.9%) 1 1/85 (1.2%) 1
    Metabolism and nutrition disorders
    ANOREXIA 0/39 (0%) 0 0/40 (0%) 0 3/35 (8.6%) 3 0/85 (0%) 0
    GOUT 2/39 (5.1%) 2 0/40 (0%) 0 0/35 (0%) 0 1/85 (1.2%) 1
    HYPERCHOLESTEROLAEMIA 3/39 (7.7%) 3 1/40 (2.5%) 1 0/35 (0%) 0 2/85 (2.4%) 2
    HYPERTRIGLYCERIDAEMIA 5/39 (12.8%) 5 2/40 (5%) 2 1/35 (2.9%) 1 5/85 (5.9%) 6
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 2/39 (5.1%) 2 1/40 (2.5%) 1 2/35 (5.7%) 3 5/85 (5.9%) 5
    BACK PAIN 2/39 (5.1%) 2 1/40 (2.5%) 1 3/35 (8.6%) 3 5/85 (5.9%) 7
    FLANK PAIN 1/39 (2.6%) 1 0/40 (0%) 0 2/35 (5.7%) 2 0/85 (0%) 0
    MUSCLE SPASMS 0/39 (0%) 0 2/40 (5%) 2 3/35 (8.6%) 3 1/85 (1.2%) 2
    MUSCULAR WEAKNESS 0/39 (0%) 0 0/40 (0%) 0 2/35 (5.7%) 2 1/85 (1.2%) 1
    MUSCULOSKELETAL PAIN 0/39 (0%) 0 1/40 (2.5%) 1 3/35 (8.6%) 3 1/85 (1.2%) 2
    MYALGIA 3/39 (7.7%) 3 1/40 (2.5%) 1 1/35 (2.9%) 1 2/85 (2.4%) 4
    PAIN IN EXTREMITY 1/39 (2.6%) 1 0/40 (0%) 0 3/35 (8.6%) 4 2/85 (2.4%) 2
    Nervous system disorders
    DIZZINESS 5/39 (12.8%) 5 1/40 (2.5%) 1 4/35 (11.4%) 5 1/85 (1.2%) 1
    HEADACHE 5/39 (12.8%) 5 3/40 (7.5%) 4 7/35 (20%) 8 7/85 (8.2%) 10
    HYPOAESTHESIA 1/39 (2.6%) 1 0/40 (0%) 0 2/35 (5.7%) 3 0/85 (0%) 0
    Psychiatric disorders
    DEPRESSION 3/39 (7.7%) 3 4/40 (10%) 4 6/35 (17.1%) 6 3/85 (3.5%) 3
    INSOMNIA 0/39 (0%) 0 3/40 (7.5%) 3 2/35 (5.7%) 2 5/85 (5.9%) 7
    Respiratory, thoracic and mediastinal disorders
    COUGH 2/39 (5.1%) 2 5/40 (12.5%) 7 2/35 (5.7%) 2 7/85 (8.2%) 10
    DYSPNOEA 0/39 (0%) 0 0/40 (0%) 0 2/35 (5.7%) 2 1/85 (1.2%) 1
    PHARYNGOLARYNGEAL PAIN 3/39 (7.7%) 3 2/40 (5%) 2 0/35 (0%) 0 0/85 (0%) 0
    RHINORRHOEA 0/39 (0%) 0 4/40 (10%) 5 0/35 (0%) 0 0/85 (0%) 0
    SLEEP APNOEA SYNDROME 2/39 (5.1%) 2 0/40 (0%) 0 0/35 (0%) 0 0/85 (0%) 0
    Skin and subcutaneous tissue disorders
    DERMATITIS 3/39 (7.7%) 3 0/40 (0%) 0 0/35 (0%) 0 1/85 (1.2%) 1
    SEBORRHOEIC DERMATITIS 2/39 (5.1%) 2 2/40 (5%) 2 1/35 (2.9%) 1 3/85 (3.5%) 3
    SKIN NODULE 2/39 (5.1%) 4 0/40 (0%) 0 2/35 (5.7%) 2 0/85 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The investigator agrees not to publish or publicly present any interim results of the study without the prior written consent of the sponsor. The investigator further agrees to provide to the sponsor 45 days prior to submission for publication or for presentation, review copies of the publication or presentation for review and comment on the data analysis and presentation including proprietary information, the accuracy of the information, and to ensure compliance with FDA regulations.

    Results Point of Contact

    Name/Title Senior Vice President, Global Clinical Development
    Organization Merck Sharp & Dohme Corp.
    Phone 1-800-672-6372
    Email ClinicalTrialsDisclosure@merck.com
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT00243230
    Other Study ID Numbers:
    • P03672
    • 2005-001057-21
    • MK-7690-020
    • P03672
    First Posted:
    Oct 21, 2005
    Last Update Posted:
    Jun 8, 2021
    Last Verified:
    May 1, 2021