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Trial record 1 of 1 for:    NCT00827112
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A Pilot Study Of A Novel Treatment Regimen, Maraviroc + Ritonavir Boosted Atazanavir, In Treatment Naive HIV-Infected Patients

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ClinicalTrials.gov Identifier: NCT00827112
Recruitment Status : Completed
First Posted : January 22, 2009
Results First Posted : November 24, 2011
Last Update Posted : June 15, 2012
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
ViiV Healthcare

Tracking Information
First Submitted Date  ICMJE January 21, 2009
First Posted Date  ICMJE January 22, 2009
Results First Submitted Date  ICMJE July 11, 2011
Results First Posted Date  ICMJE November 24, 2011
Last Update Posted Date June 15, 2012
Study Start Date  ICMJE March 2009
Actual Primary Completion Date July 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 19, 2011)
Percentage of Participants With Plasma Human Immuno Deficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) Levels Less Than 50 Copies/Milliliter (mL) [ Time Frame: Week 48 ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 21, 2009)
The percentage of patients with plasma HIV-1 RNA <50 copies/mL in each treatment arm at 48 weeks [ Time Frame: Week 48 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 8, 2012)
  • HIV-1 RNA Levels at Baseline [ Time Frame: Baseline ]
  • Change From Baseline in HIV-1 RNA Levels of First 15 Participants at Days 4, 7, 10 and 14 [ Time Frame: Baseline , Days 4, 7, 10 and 14 ]
    Plasma HIV-1 RNA levels were evaluated for first 15 participants enrolled at United States (U.S) sites only.
  • Maximum Observed Plasma Concentration (Cmax) of Maraviroc [ Time Frame: Day 14 (0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose) ]
  • Minimum Observed Plasma Concentration (Cmin) of Maraviroc [ Time Frame: Day 14 (0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose) ]
  • Average Observed Plasma Concentration (Cavg) of Maraviroc [ Time Frame: Day 14 (0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose) ]
    Cavg was described as area under the plasma concentration-time profile from time zero to time 24 hours (AUC24) divided by the dosing interval (AUC24/ 24).
  • Change From Baseline in Plasma log10 Viral Load at Weeks 16, 24, 48 and 96 [ Time Frame: Baseline, Week 16, Week 24, Week 48, Week 96 ]
  • Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA [ Time Frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, Week 96 ]
  • Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA [ Time Frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, Week 96 ]
  • Time to Loss of Virological Response (TLOVR) [ Time Frame: Baseline through Week 96 ]
    TLOVR (virological failure) was defined as the time from first dose of study treatment (Day 1) until the time of virologic failure using the time to loss of virologic response algorithm.
  • Time-Averaged Difference (TAD) in log10 Viral Load [ Time Frame: Week 16, Week 24, Week 48, Week 96 ]
    TAD was calculated as area under the curve of HIV divided by time period minus baseline HIV where HIV was denoted as HIV-1 RNA (log10 copies/mL).
  • Change From Baseline in Cluster of Differentiation 4+T Lymphocyte (CD4) Cell Counts at Weeks 16, 24, 48 and 96 [ Time Frame: Baseline, Week 16, Week 24, Week 48, Week 96 ]
  • Change From Baseline in Cluster of Differentiation 8+T Lymphocyte (CD8) Cell Count at Weeks 16, 24, 48 and 96 [ Time Frame: Baseline, Week 16, Week 24, Week 48, Week 96 ]
  • Number of Participants With Genotypic Resistance [ Time Frame: Week 96 or Time of treatment failure ]
    Genotypic resistance was assessed for all participants at screening and was evaluated for protease inhibitors (PIs), Nucleotide reverse transcriptase inhibitors (NRTIs), and non-NRTIs (NNRTIs) using Monogram GenoSeq and/or PhenoSenseGT assays. This was then repeated for all participants with HIV-1 viral load more than 500 copies/mL either at treatment failure or at early termination, up to Week 96.
  • Number of Participants With Phenotypic Resistance [ Time Frame: Week 96 or Time of treatment failure ]
    Phenotypic resistance was assessed for all participants at screening and was evaluated for PIs, NRTIs, and NNRTIs using Monogram GenoSeq and/or PhenoSenseGT assays. This was then repeated for all participants with HIV-1 viral load more than 500 copies/mL either at treatment failure or at early termination, up to Week 96.
  • Number of Participants With HIV-1 RNA Tropism Status Using Trofile Assay [ Time Frame: Baseline to Week 96 or Time of treatment Failure ]
    Viral tropism was determined using the trofile assay with enhanced sensitivity for participants with HIV-1 RNA greater than equal to 1000 copies/mL. The enhanced trofile assay had the sensitivity to detect 100 percent of spiked samples when C-X-C chemokine receptor type 4 {CXCR4} [X4]-using HIV-1 RNA represented 0.3 percent of the total viral population.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 21, 2009)
  • Safety and tolerability of the treatment with novel combinations of maraviroc (Selzentry, Celsentri with atazanavir/ritonavir; and another combination regimen (atazanavir and emtricitabine/tenofovir) in treatment-naïve HIV-1 infected subjects [ Time Frame: Throughout the study ]
  • Plasma HIV RNA of the first 15 patients enrolled in two treatment arms at Days 4, 7, 10, and 14 (in US sites only) [ Time Frame: Days 4, 7, 10, and 14 ]
  • PK of maraviroc of the patients enrolled in maraviroc arm [ Time Frame: Day 15 ]
  • Virological Response [ Time Frame: wk 16,24,48 ]
  • Immunological Response [ Time Frame: wk 16,24,48 ]
  • Evolution of viral resistance and tropism [ Time Frame: at the time of treatment failure ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Pilot Study Of A Novel Treatment Regimen, Maraviroc + Ritonavir Boosted Atazanavir, In Treatment Naive HIV-Infected Patients
Official Title  ICMJE Pilot Study Of Novel Combination Of Maraviroc + Atazanavir/Ritonavir vs. Atazanavir/Ritonavir + Emtricitabine/Tenofovir For The Treatment Of Naïve HIV-Infected Patients With R5 HIV-1
Brief Summary This is a pilot study to examine if the novel treatment regimen maraviroc plus boosted atazanavir can be expected to be safe and efficacious in treatment naive HIV infected patients. Based on the results from this study, a confirmatory phase 3 study may be conducted.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Human Immunodeficiency Virus-1
Intervention  ICMJE
  • Drug: maraviroc
    maraviroc (Selzentry, Celsentri) 150mg QD + atazanavir (Reyataz) /ritonavir (Norvir) (300/100mg) QD OR maraviroc (Selzentry, Celsentri) 150mg QD+ darunavir (Prezista)/ritonavir (Norvir) (800/100 mg) QD (if atazanavir (Reyataz) /ritonavir (Norvir) is replaced by darunavir (Prezista)/ritonavir (Norvir)) OR maraviroc (Selzentry, Celsentri) 150mg QD+ lopinavir/ritonavir (Kaletra, Aluvia) (400/100 mg) BID (if atazanavir (Reyataz) /ritonavir (Norvir) is replaced by lopinavir/ritonavir (Kaletra, Aluvia))
    Other Name: maraviroc =Celsentri, Selzentry; atazanavir =Reyataz; ritonavir =Norvir; lopinavir/ritonavir=Kaletra, Aluvia; darunavir=Prezista
  • Drug: maraviroc
    emtricitabine/tenofovir (Truvada) 200/300mg QD + atazanavir (Reyataz) /ritonavir (Norvir) 300/100 mg QD OR emtricitabine/tenofovir (Truvada) 200/300 mg QD + darunavir (Prezista)/ritonavir (Norvir) (800/100 mg) QD (if atazanavir (Reyataz) /ritonavir (Norvir) is replaced by darunavir (Prezista)/ritonavir (Norvir)) OR emtricitabine/tenofovir (Truvada) 200/300 mg QD + lopinavir/ritonavir(Kaletra, Aluvia) (400/100 mg) BID (if atazanavir (Reyataz) /ritonavir (Norvir) is replaced by lopinavir/ritonavir (Kaletra, Aluvia))
    Other Name: maraviroc=Celsentri, Selzentry; emtricitabine/tenofovir=Truvada; atazanavir =Reyataz; ritonavir =Norvir; lopinavir/ritonavir=Kaletra, Aluvia
Study Arms  ICMJE
  • Experimental: Arm A
    maraviroc (Selzentry, Celsentri) 150 mg QD + atazanavir (Reyataz) /ritonavir (Norvir) 300/100mg QD Subjects experiencing unconjugated hyperbilirubinemia attributable to atazanavir (Reyataz) /ritonavir (Norvir) without any other etiology of hyperbilirubinemia, responding to the therapy without virologic failure, but expressing cosmetic concerns because of the jaundice or scleral icterus (associated with bilirubin elevations) and wish to discontinue atazanavir (Reyataz) in spite of reassurances by the investigator, will be permitted on a single occasion only to switch to another protease inhibitor either darunavir (Prezista)/ritonavir (Norvir)((800/100 mg) QD or lopinavir/ritonavir (Kaletra, Aluvia)(400/100mg) BID and remain in the study. If the investigator decides to switch to a protease inhibitor other than darunavir (Prezista)/ritonavir (Norvir) or lopinavir/ritonavir (Kaletra, Aluvia)(, then the subject must be discontinued from the study.
    Intervention: Drug: maraviroc
  • Experimental: Arm B

    emtricitabine/tenofovir (Truvada) 200/300mg QD + atazanavir (Reyataz) /ritonavir (Norvir) 300/100 mg QD

    Subjects experiencing unconjugated hyperbilirubinemia attributable to atazanavir (Reyataz) /ritonavir (Norvir) without any other etiology of hyperbilirubinemia, responding to the therapy without virologic failure, but expressing cosmetic concerns because of the jaundice or scleral icterus (associated with bilirubin elevations) and wish to discontinue atazanavir in spite of reassurances by the investigator, will be permitted on a single occasion only to switch to another protease inhibitor either darunavir/ritonavir (800/100 mg) QD or lopinavir/ritonavir (400/100mg) BID and remain in the study. If the investigator decides to switch to a protease inhibitor other than darunavir/ritonavir or lopinavir/ritonavir, then the subject must be discontinued from the study.

    Intervention: Drug: maraviroc
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 8, 2012)
129
Original Estimated Enrollment  ICMJE
 (submitted: January 21, 2009)
88
Actual Study Completion Date  ICMJE July 2011
Actual Primary Completion Date July 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • HIV-1 RNA viral load of ≥1,000 copies/mL measured at the Screening Visit.
  • CD4 count ≥100 cells/mm3 at Screening.
  • Have only R5 HIV-1 at Screening as verified by the Monogram Bioscience Trofile® assay with enhanced sensitivity.

Exclusion Criteria:

  • Prior treatment with any other HIV antiretroviral therapy for more than 14 days at any time.
  • Any evidence of resistance to atazanavir, tenofovir, and emtricitabine.
  • X4-or dual/mixed-tropic virus by enhanced Trofile assay or repeated assay failure or not reportable results.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00827112
Other Study ID Numbers  ICMJE A4001078
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party ViiV Healthcare
Study Sponsor  ICMJE ViiV Healthcare
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account ViiV Healthcare
Verification Date June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP