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A Pilot Study Of A Novel Treatment Regimen, Maraviroc + Ritonavir Boosted Atazanavir, In Treatment Naive HIV-Infected Patients
This study has been completed.

First Received on January 21, 2009.   Last Updated on October 19, 2011   History of Changes
Sponsor: ViiV Healthcare
Collaborator: Pfizer
Information provided by (Responsible Party): ViiV Healthcare
ClinicalTrials.gov Identifier: NCT00827112
  Purpose

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.


Condition Intervention Phase
Human Immunodeficiency Virus-1
 Drug: maraviroc
 Phase II

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency
MedlinePlus related topics: HIV/AIDS
Drug Information available for: Tenofovir Ritonavir Lopinavir BMS 232632 Tenofovir disoproxil Tenofovir Disoproxil Fumarate Darunavir Atazanavir sulfate Maraviroc Darunavir ethanolate Truvada
U.S. FDA Resources

Further study details as provided by ViiV Healthcare:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • HIV-1 RNA Levels at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
    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 and 48 [ Time Frame: Baseline, weeks 16, 24 and 48 ] [ Designated as safety issue: No ]
  • Change From Baseline in Plasma log10 Viral Load at Week 96 [ Time Frame: Baseline and Week 96 ] [ Designated as safety issue: No ]
  • Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA [ Time Frame: Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48 ] [ Designated as safety issue: No ]
  • Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
  • Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA [ Time Frame: Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48 ] [ Designated as safety issue: No ]
  • Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
  • Time to Loss of Virological Response (TLOVR) [ Time Frame: Baseline through Week 96 ] [ Designated as safety issue: No ]
    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: Weeks 16, 24 and 48 ] [ Designated as safety issue: No ]
    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).

  • Time-Averaged Difference (TAD) in log10 Viral Load at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, weeks 16, 24 and 48 ] [ Designated as safety issue: No ]
  • Change From Baseline in Cluster of Differentiation 4+T Lymphocyte (CD4) Cell Counts at Week 96 [ Time Frame: Baseline and Week 96 ] [ Designated as safety issue: No ]
  • Change From Baseline in Cluster of Differentiation 8+T Lymphocyte (CD8) Cell Count [ Time Frame: Baseline and weeks 16, 24 and 48 ] [ Designated as safety issue: No ]
  • Change From Baseline in Cluster of Differentiation 8+T Lymphocyte (CD8) Cell Count at Week 96 [ Time Frame: Baseline and Week 96 ] [ Designated as safety issue: No ]
  • Number of Participants With Genotypic Resistance [ Time Frame: Week 48 or Time of treatment failure ] [ Designated as safety issue: No ]
    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 48.

  • Number of Participants With Phenotypic Resistance [ Time Frame: Week 48 or Time of treatment failure ] [ Designated as safety issue: No ]
    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 48.

  • Number of Participants With HIV-1 RNA Tropism Status Using Trofile Assay [ Time Frame: Baseline to week 48 or Time of treatment Failure ] [ Designated as safety issue: No ]
    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.


Enrollment: 121
Study Start Date: March 2009
Study Completion Date: July 2011
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
 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
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.

 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

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00827112

  Show 39 Study Locations
Sponsors and Collaborators
ViiV Healthcare
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
To obtain contact information for a study center near you, click here.  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT00827112     History of Changes
Other Study ID Numbers: A4001078
Study First Received: January 21, 2009
Results First Received: July 11, 2011
Last Updated: October 19, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by ViiV Healthcare:
CCR5-tropic HIV-1 virus

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Ritonavir
Lopinavir
Atazanavir
Darunavir
 Tenofovir
Tenofovir disoproxil
Emtricitabine
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012



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