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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01345630




Registration number
NCT01345630
Ethics application status
Date submitted
27/04/2011
Date registered
2/05/2011
Date last updated
14/01/2016

Titles & IDs
Public title
Comparative Trial Of Maraviroc Versus Emtricitabine/Tenofovir Both With Darunavir/Ritonavir In Antiretroviral-Naive Patients Infected With CCR5 Tropic HIV 1
Scientific title
A Multicenter, Randomized, Double-Blind, Comparative Trial Of Maraviroc + Darunavir/Ritonavir Versus Emtricitabine/Tenofovir + Darunavir/Ritonavir For The Treatment Of Antiretroviral-Naive Hiv-Infected Patients With Ccr5-Tropic Hiv-1
Secondary ID [1] 0 0
2010-021785-30
Secondary ID [2] 0 0
A4001095
Universal Trial Number (UTN)
Trial acronym
MODERN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV-1 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Maraviroc
Treatment: Drugs - Emtricitabine/tenofovir
Treatment: Drugs - darunavir/ritonavir 800/100 mg
Treatment: Drugs - placebo for emtricitabine/tenofovir
Treatment: Drugs - placebo for maraviroc

Experimental: Maraviroc - Maraviroc 150 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for emtricitabine/tenofovir once daily.

Active Comparator: Emtricitabine/tenofovir - Emtricitabine/tenofovir 200/300 mg once daily plus darunavir/ritonavir 800/100 mg once daily plus placebo for maraviroc once daily.


Treatment: Drugs: Maraviroc
Maraviroc tablet 150 mg once daily for 96 weeks.

Treatment: Drugs: Emtricitabine/tenofovir
Emtricitabine/tenofovir tablet 200/300 mg once daily for 96 weeks.

Treatment: Drugs: darunavir/ritonavir 800/100 mg
darunavir/ritonavir 800/100 mg

Treatment: Drugs: placebo for emtricitabine/tenofovir
placebo for emtricitabine/tenofovir

Treatment: Drugs: placebo for maraviroc
placebo for maraviroc

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL. - The proportion of participants who achieved HIV-1 RNA <50 copies/mL at week 48 was assessed according to Food and Drug Administration's (FDA's) Missing, Switch, Discontinuation'=Failure (MSDF) Snapshot algorithm. The algorithm used the plasma HIV-1 RNA in the Week 48 visit window, followed the "virology-first principle" and considers a participant who has a missing plasma HIV-1 RNA, or switches to prohibited ARV regimen or discontinues from the study or study drug for any reason, or dies, as a failure.
Timepoint [1] 0 0
Week 48
Secondary outcome [1] 0 0
Frequency of Adverse Events (AE). - Number of participants with treatment-emergent non serious AEs
Timepoint [1] 0 0
Week 96
Secondary outcome [2] 0 0
Number of Participants With Grade 3 or 4 AEs - Number of participants with grade 3 or 4 AEs are presented here.
Timepoint [2] 0 0
Week 96
Secondary outcome [3] 0 0
Number of Participants Who Discontinued Due to AEs - Number of participants who discontinued due to AEs are reported here. Three participants (two from the MVC+DRV/r arm and one from the FTC/TDF+DRV/r arm) were not considered as discontinued due to AE because other reasons for discontinuation were prioritized for these participants.
Timepoint [3] 0 0
Week 96
Secondary outcome [4] 0 0
Number of Treatment-related AEs - Number of treatment-related AEs are presented here.
Timepoint [4] 0 0
Week 96
Secondary outcome [5] 0 0
Number of Participants With Treatment-emergent Serious Adverse Events - Total number of participants with treatment-emergent serious adverse events are reported
Timepoint [5] 0 0
Week 96
Secondary outcome [6] 0 0
Number of Participants With Abnormal Laboratory Values - Number of participants with laboratory abnormalities are reported
Timepoint [6] 0 0
Week 96
Secondary outcome [7] 0 0
Severity of Abnormal Laboratory Values - Number of participants who had clinically significant laboratory abnormalities of Grade 3 and Grade 4 according to DAIDS. Abnormality incidence of highest grade was reported for a labcode for each individual participant.
Timepoint [7] 0 0
Week 96
Secondary outcome [8] 0 0
The Relationship Between the Proportion of Participants With Plasma HIV-1 RNA <50 Copies/mL at the Week 48 and the Screening Tropism Test (Genotype Test or ESTA). - The relationship of the proportion of participants achieving HIV-1 RNA <50 copies/mL at Week 48 with the screening tropism test for the MVC containing regimen was analyzed. Virologic response for a participant at Week 48 was derived using the FDA's Snapshot MSDF algorithm. Difference in proportions of patients with plasma HIV-1 RNA <50 copies/mL at week 48 between the maraviroc and the emtricitabine/tenofovir treatment arms, with two-sided 95% confidence interval, among patients who are R5 by genotype (including some who were originally randomized to ESTA and are R5 by genotype upon retesting), were calculated via the Maximum Likelihood method. The estimate was adjusted for the screening plasma HIV RNA level (<100,000 vs. =100,000) copies/mL via the Mantel Haenszel (MH) method.
Timepoint [8] 0 0
Week 48
Secondary outcome [9] 0 0
Virologic Outcomes at Week 48 Using Protocol-Defined Treatment Failure (PDTF). - Per the protocol participants who meet the following criteria were regarded as PDTFs requiring a confirmatory plasma HIV-1 RNA determination: • Decrease in plasma HIV-1 RNA <1 log10 from baseline after Week 4 unless plasma HIV-1 RNA is <50 copies/mL, or • Plasma HIV-1 RNA >1.0 log10 above the nadir value after Week 4 where the nadir is the lowest plasma HIV-1 RNA concentration, or • Plasma HIV-1 RNA =50 copies/mL at any time after Week 24, or • Plasma HIV-1 RNA =50 copies/mL after suppression to <50 copies/mL on two consecutive visits, or • Decrease in plasma HIV-1 RNA =2 log10 from baseline on or after Week 12 unless plasma HIV-1 RNA is <400 copies/mL. Decrease in plasma HIV-1 RNA =2 log10 from baseline on or after Week 12 unless plasma HIV-1 RNA is <50 copies/mL (before August 30 2012) or <400 copies/mL (after August 30 2012).
Timepoint [9] 0 0
Week 48
Secondary outcome [10] 0 0
Tropism Change Between Screening or Baseline and PDTF - For participants meeting the PDTF criteria, tropism was assessed using the original randomized and alternate assays (ie, both genotype testing and ESTA). Data reported here corresponds to the timepoint at or after PDTF.
Timepoint [10] 0 0
Week 48
Secondary outcome [11] 0 0
Number of Participants With Viral Resistance to Maraviroc (Maraviroc Treated Participants Only) in Participants Meeting PDTF Criteria. - For participants meeting the PDTF criteria, viral resistance to maraviroc for maraviroc treated participants was assessed in patients with R5 virus at failure. The resistance level is calculated by reference to a laboratory strain of virus that is analyzed in parallel with the clinical isolate to identify 50% inhibitory concentrations (IC50). The maximal percent inhibition is the percent inhibition that is achieved in a titration of the drug at high concentrations when the addition of more drug does not result in increased inhibition. Maximal percent inhibition is obtained in the same way as the titration for IC50, but the key measure is of the plateau height of percent inhibition, where increased concentration of maraviroc does not result in additional inhibition. This is consistent with the virus developing some ability to use maraviroc-bound CCR5 for entry. A significant change in IC50 is not required for this mechanism.
Timepoint [11] 0 0
Week 48
Secondary outcome [12] 0 0
Number of Participants With Resistance to Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTI), Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI), and Protease Inhibitors (PI) in Participants Meeting PDTF Criteria - For participants meeting the PDTF criteria, viral resistance (both genotypic and phenotypic) to NRTI, NNRTI, and PI's were assessed at Baseline and on-treatment. The assessment was performed using the overall (i.e. net) susceptibility score provided using the PhenoSense GT assay. The number of participants with successful assessments were 15/17 for the MVC+DRV/r arm and 3/3 for the FTC/TDF+DRV/r arm.
Timepoint [12] 0 0
Week 48
Secondary outcome [13] 0 0
Absolute Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Marker Cluster of Differentiation 4 (CD4, Cell/mm^3) - The differences in the magnitude of changes in CD4+ at Baseline and at Week 48 for maraviroc versus emtricitabine/tenofovir were compared.
Timepoint [13] 0 0
Baseline, Week 48
Secondary outcome [14] 0 0
Percent Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Activation Marker CD4 (%) - The differences in the magnitude of changes in CD4+ from Baseline through Week 48 for maraviroc versus emtricitabine/tenofovir were compared.
Timepoint [14] 0 0
Baseline, Week 48
Secondary outcome [15] 0 0
Absolute Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Marker Cluster of Differentiation 8 (CD8, Cell/mm^3) - The differences in the magnitude of changes in CD8+ cell counts from baseline through Week 48 for maraviroc versus emtricitabine/tenofovir were compared.
Timepoint [15] 0 0
Baseline, Week 48
Secondary outcome [16] 0 0
Percent Change From Baseline in Immune Cell Function at Week 48: Lymphocyte Activation Marker CD8 (%) - The differences in the magnitude of changes in CD8+ cell counts from Baseline through Week 48 for maraviroc versus emtricitabine/tenofovir were compared.
Timepoint [16] 0 0
Baseline, Week 48
Secondary outcome [17] 0 0
Absolute Change in CD4+/CD8+ Ratio From Baseline to Week 48 - The differences in the magnitude of changes in CD4+/CD8+ ratio from Baseline through Weeks 48 for maraviroc versus emtricitabine/tenofovir were compared.
Timepoint [17] 0 0
Baseline, Week 48
Secondary outcome [18] 0 0
Changes in Peripheral Fat Distribution Using Dual Energy X-ray Absorptiometry [DEXA] Scan From Baseline and at Week 48. - A sub-study was conducted in which the participants underwent whole-body DEXA scans to evaluate peripheral fat tissue estimates for left and right arms and legs and truncal fat mass and truncal lean mass. Truncal abdominal fat were estimated from the DEXA scan field set on the torso. The effects on estimates of fat mass and lean mass were addressed by providing LSMs of change from baseline.
Timepoint [18] 0 0
Week 48
Secondary outcome [19] 0 0
Changes in Trunk to Limb Fat Distribution Using DEXA Scan From Baseline and at Week 48 - A sub-study was conducted in which the participants underwent whole-body DEXA scans to evaluate peripheral fat tissue estimates for left and right arms and legs and truncal fat mass and truncal lean mass. Truncal abdominal fat were estimated from the DEXA scan field set on the torso. The effects on estimates of fat mass and lean mass were addressed by providing LSMs of change from baseline.
Timepoint [19] 0 0
Week 48
Secondary outcome [20] 0 0
Changes in Bone Mineral Density (Using DEXA Scan and Serum Markers) From Baseline and at Week 48 - Total Hip BMD - Bone mineral density was evaluated by DEXA scan in a subset of participants who consented to these evaluations. The effects on BMD were addressed by providing LSMs of change from baseline bone mineral density of the lumbar spine (L1-L4), left total hip and femoral neck as measured by the DEXA scan.
Timepoint [20] 0 0
Week 48
Secondary outcome [21] 0 0
Changes in Bone Mineral Density (Using DEXA Scan and Serum Markers) From Baseline and at Week 48 - Femoral Neck BMD - Bone mineral density was evaluated by DEXA scan in a subset of participants who consented to these evaluations. The effects on BMD were addressed by providing LSMs of change from Baseline bone mineral density femoral neck as measured by the DEXA scan.
Timepoint [21] 0 0
Week 48
Secondary outcome [22] 0 0
Changes in Bone Mineral Density (Using DEXA Scan and Serum Markers) From Baseline and at Week 48 - AP Lumbar Spine (L1 - L4) BMD - Bone mineral density was evaluated by DEXA scan in a subset of participants who consented to these evaluations. The effects on BMD were addressed by providing LSMs of change from baseline bone mineral density of the lumbar spine (L1-L4) as measured by the DEXA scan.
Timepoint [22] 0 0
Week 48
Secondary outcome [23] 0 0
Change in Bone Turnover Markers From Baseline and at Week 48 - Blood Osteocalcin - Bone turnover marker, osteocalcin, was collected in the subset of participants participating in the DEXA scan sub-study.
Timepoint [23] 0 0
Week 48
Secondary outcome [24] 0 0
Change in Bone Turnover Markers From Baseline and at Week 48 - Type 1 Collagen Peptide (CTX-1) - Bone turnover marker, C-telopeptide of type 1 collagen (CTx), was collected in the subset of participants participating in the DEXA scan sub-study.
Timepoint [24] 0 0
Week 48

Eligibility
Key inclusion criteria
- Plasma HIV-1 RNA equal to or greater than 1,000 copies/mL measured at the Screening
Visit.

- CD4 count equal to or greater than 100 cells/mm3 at Screening.

- Have only R5 HIV 1 at Screening as verified by a randomized tropism assay.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior treatment with any other HIV antiretroviral therapy for more than 14 days at any
time.

- Any evidence of genotypic/phenotypic resistance to darunavir, tenofovir, and
emtricitabine.

- CXCR4 using virus detected using randomized tropism determination or repeated failure
to obtain an interpretable tropism result.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
East Sydney Doctors - Darlinghurst
Recruitment hospital [2] 0 0
Holdsworth House General Practice - Darlinghurst
Recruitment hospital [3] 0 0
St Vincent's Hospital - Darlinghurst
Recruitment hospital [4] 0 0
Taylor Square Private Clinic - Surry Hills
Recruitment hospital [5] 0 0
Brisbane Sexual Health and HIV Service - Brisbane
Recruitment hospital [6] 0 0
Melbourne Sexual Health Centre - Carlton
Recruitment hospital [7] 0 0
Clinical Research Unit, Infectious Diseases - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2010 - Surry Hills
Recruitment postcode(s) [3] 0 0
4000 - Brisbane
Recruitment postcode(s) [4] 0 0
3053 - Carlton
Recruitment postcode(s) [5] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
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California
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United States of America
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Colorado
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United States of America
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Connecticut
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United States of America
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District of Columbia
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United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
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Iowa
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United States of America
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Louisiana
Country [11] 0 0
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Massachusetts
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Michigan
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Minnesota
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Missouri
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Nebraska
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New Jersey
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New York
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North Carolina
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Ohio
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Texas
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Washington
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Austria
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Wien
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Belgium
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Antwerpen
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Belgium
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Brussels
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Belgium
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Bruxelles
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Belgium
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Gent
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Belgium
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Liege
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Canada
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British Columbia
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Canada
State/province [29] 0 0
Ontario
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Canada
State/province [30] 0 0
Quebec
Country [31] 0 0
Denmark
State/province [31] 0 0
Hvidovre
Country [32] 0 0
Denmark
State/province [32] 0 0
Koebenhavn OE
Country [33] 0 0
Denmark
State/province [33] 0 0
Odense
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Finland
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Helsinki
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France
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Cedex 02
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France
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Cedex 12
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France
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Cedex 18
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France
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Bordeaux cedex
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France
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Creteil
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France
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Le Kremlin Bicetre
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France
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LYON Cedex 4
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France
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Montpellier
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France
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Nantes
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Paris Cedex 10
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France
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Paris
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France
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Strasbourg Cedex
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France
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Tourcoing
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Germany
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Berlin
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Germany
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Bonn
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Germany
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Frankfurt am Main
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Germany
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Hamburg
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Germany
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Koeln
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Germany
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Muenchen
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Hungary
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Budapest
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Italy
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Milano
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Netherlands
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Utrecht
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Poland
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Bydgoszcz
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Poland
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Warszawa
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Poland
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Wroclaw
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Portugal
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Amadora
Country [61] 0 0
Portugal
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Lisboa
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Portugal
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Porto
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Puerto Rico
State/province [63] 0 0
Bayamon
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Puerto Rico
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Ponce
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Puerto Rico
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Rio Piedras
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Puerto Rico
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San Juan
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Spain
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Barcelona
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Spain
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Alicante
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Spain
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Cordoba
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Spain
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Madrid
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Spain
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Sevilla
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Sweden
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Goteborg
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Sweden
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Malmo
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Sweden
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Stockholm
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Switzerland
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Basel
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Switzerland
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Bern
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Switzerland
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St. Gallen
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Switzerland
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Zurich
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United Kingdom
State/province [79] 0 0
Birmingham
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United Kingdom
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Brighton
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United Kingdom
State/province [81] 0 0
Edinburgh
Country [82] 0 0
United Kingdom
State/province [82] 0 0
London
Country [83] 0 0
United Kingdom
State/province [83] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
ViiV Healthcare
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Pfizer
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to assess whether maraviroc administered once daily is
non-inferior to emtricitabine/tenofovir also administered once daily each in combination with
darunavir/ritonavir in the treatment of antiretroviral-naive patients as evaluated at Week 48
of treatment.
Trial website
https://clinicaltrials.gov/show/NCT01345630
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT01345630