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A Phase 2B Multicenter, Randomized, Comparative Trial Of UK-453,061 Versus Etravirine In Combination With Darunavir/Ritonavir And A Nucleos(t)Ide Reverse Transcriptase Inhibitor For The Treatment Of Antiretroviral Experienced HIV-1 Infected Subjects With Evidence Of NNRTI Resistant HIV-1

This study has been terminated.
(See termination reason in detailed description.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00823979
First received: January 15, 2009
Last updated: March 24, 2014
Last verified: March 2014

January 15, 2009
March 24, 2014
March 2009
October 2012   (final data collection date for primary outcome measure)
Percentage of Participants With Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) Levels Less Than (<) 50 Copies/Milliliter (mL) at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5).
Percentage of subjects with HIV-1 RNA <48 copies/mL at 24 weeks. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00823979 on ClinicalTrials.gov Archive Site
  • Percentage of Participants With HIV-1 RNA Levels <50 Copies/mL at Week 48 and 96 [ Time Frame: Weeks 48, 96 ] [ Designated as safety issue: No ]
    Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5).
  • Percentage of Participants With HIV-1 RNA Levels <400 Copies/mL at Week 24, 48 and 96 [ Time Frame: Week 24, 48, 96 ] [ Designated as safety issue: No ]
    Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5).
  • Change From Baseline in log10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96 [ Time Frame: Baseline, Week 24, 48, 96 ] [ Designated as safety issue: No ]
    Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5). For the log10 scale, all the HIV-1 RNA levels were log10 transformed prior to the average calculations. Baseline value calculated as average of measurements collected prior to and including Day 1 pre-dose.
  • Time-Averaged Difference (TAD) in log10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96 [ Time Frame: Week 24, 48, 96 ] [ Designated as safety issue: No ]
    TAD was calculated as (area under the curve of HIV-1 RNA levels [log10 copies/mL] from baseline to the time point of interest divided by time period in weeks) minus baseline HIV-1 RNA level (log10 copies/mL). Baseline value calculated as average of measurements collected at prior to and including Day 1 pre-dose. Due to early termination of the study decision was made not to derive TAD results for Week 96.
  • Percentage of Participants With Response as Determined by the Time to Loss of Virologic Response (TLOVR50) Algorithm at Week 24, 48 and 96 [ Time Frame: Week 24, 48, 96 ] [ Designated as safety issue: No ]
    TLOVR50 response (50 denotes lower limit of quantification [LLOQ] of assay=50 copies/mL): compliment to TLOVR50 failure. TLOVR50 failure based on observed HIV-1 RNA levels and failure events (death; permanent discontinuation of drug; lost to follow-up; new ARV drug; met treatment failure [TF] criteria). TF: an increase of at least (>=)3 times the baseline plasma HIV-1 RNA level at Week 2 or thereafter; failure to achieve HIV-1 RNA level <50 copies/mL at Week 24; starting at Week 2, an increase in HIV-1 RNA level to detectable levels (>50 copies/mL); HIV-1 RNA <1 log10 decrease from baseline at Week 4 or thereafter. TF were confirmed by second measurement >=14 days after first. Baseline value was calculated as the average of the measurements collected prior to and including Day 1 pre-dose.
  • Change From Baseline in Cluster of Differentiation 4 (CD4+) Absolute Lymphocyte Counts at Week 24, 48 and 96 [ Time Frame: Baseline, Week 24, 48, 96 ] [ Designated as safety issue: No ]
    Blood samples for immunological status assessed by CD4+ lymphocyte count. Baseline value was calculated as the average of the measurements collected prior to and including Day 1 pre-dose.
  • Change From Baseline in Cluster of Differentiation 4 (CD4+) Percentage Lymphocyte Counts at Week 24, 48, 96 [ Time Frame: Baseline, Week 24, 48, 96 ] [ Designated as safety issue: No ]
    Blood samples for immunological status assessed by CD4+ lymphocyte count. Baseline value was calculated as the average of the measurements collected prior to and including Day 1 pre-dose.
  • Number of Participants With Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) Resistance-Associated Mutations (RAMs) and/or Phenotypic Susceptibility at Time of Treatment Failure Through Week 48 [ Time Frame: Baseline through Week 48 ] [ Designated as safety issue: No ]
    Genotypic and phenotypic resistance to NNRTIs based on International Acquired Immunodeficiency Syndrome (AIDS) Society, United States of America (IAS-USA) RAM guidelines were evaluated using Monogram Biosciences PhenoSenseGT Assay at Baseline. This was then repeated for all participants with HIV-1 viral load >500 copies/mL at treatment failure, up to Week 48.
  • Number of Participants With Laboratory Test Abnormalities [ Time Frame: Baseline up to Week 48 or early termination ] [ Designated as safety issue: Yes ]
    Laboratory analysis included blood chemistry, hematology and urinalysis.
  • Population Pharmacokinetics (PK) of Lersivirine [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 ] [ Designated as safety issue: No ]
    Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.
  • Lersivirine Success Percentage With Reference to Median Minimum Observed Plasma Concentration (Cmin) [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 ] [ Designated as safety issue: No ]
    Simple quartile exposure analysis of success rate (viral load <50 copies/mL) versus median Cmin assesses the exposure response relationship. Percentage of participants with HIV-1 RNA level <50 copies/mL at median Cmin quartile were planned to be reported.
  • The percentage of subjects with HIV-1 RNA <48 copies/mL and <400 copies/mL at various time points [ Time Frame: 24-96 weeks ] [ Designated as safety issue: Yes ]
  • The change from baseline in log10 transformed HIV 1 RNA levels [ Time Frame: 24-96 weeks ] [ Designated as safety issue: Yes ]
  • Assessment of Genotypic and phenotypic resistance at various time points [ Time Frame: TBD ] [ Designated as safety issue: Yes ]
  • The time-averaged difference (TAD) in log10 transformed HIV 1 RNA levels at various time points. [ Time Frame: 24-96 weeks ] [ Designated as safety issue: Yes ]
  • The percentage of subjects with virologic response at different time points. [ Time Frame: 48-96 weeks ] [ Designated as safety issue: Yes ]
  • Change from baseline in CD4+ cell counts (absolute and percentage). [ Time Frame: 24-96 weeks ] [ Designated as safety issue: Yes ]
  • Safety and tolerability as measured by spontaneous adverse event reports, serious adverse events and safety laboratory tests. [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic (PK) and pharmacokinetic/pharmacodynamic (PK/PD) analyses (to be reported separately). [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • UK-453,061 pharmacokinetic parameters AUC24, Cmax and C24h (PK sub-study). [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
A Phase 2B Multicenter, Randomized, Comparative Trial Of UK-453,061 Versus Etravirine In Combination With Darunavir/Ritonavir And A Nucleos(t)Ide Reverse Transcriptase Inhibitor For The Treatment Of Antiretroviral Experienced HIV-1 Infected Subjects With Evidence Of NNRTI Resistant HIV-1
A Phase 2B Multicenter, Randomized, Comparative Trial Of UK-453,061 Versus Etravirine In Combination With Darunavir/Ritonavir And A Nucleos(t)Ide Reverse Transcriptase Inhibitor For The Treatment Of Antiretroviral Experienced HIV-1 Infected Subjects With Evidence Of NNRTI Resistant HIV-1

This is a 96 week study to determine if UK- 453,061 in combination with Darunavir /ritonavir and a Nucleos(t)ide Reverse Transcriptase inhibitor is as efficacious, safe and tolerable as etravirine in combination with Darunavir /ritonavir and a Nucleos(t)ide Reverse Transcriptase inhibitor in HIV-1 infected patients who have been previously treated with antiretroviral drugs and have NNRTI resistance mutations.

The trial was terminated on 12 April, 2012 due to lack of efficacy at the Week 24 analysis. The decision to terminate the trial was not based on any safety concerns.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV-1
  • Drug: UK-453,061 Dose 1
    UK 453,061 750 mg QD + one optimized NRTI + darunavir/ritonavir.
  • Drug: UK-453,061 Dose 2
    UK 453,061 1000 mg QD + one optimized NRTI + darunavir/ritonavir.
  • Drug: Etravirine
    Etravirine 200 mg BID + one optimized NRTI + darunavir/ritonavir.
  • Experimental: UK- 453,061 Dose One
    Intervention: Drug: UK-453,061 Dose 1
  • Experimental: UK- 453,061 Dose Two
    Intervention: Drug: UK-453,061 Dose 2
  • Active Comparator: Comparator
    Intervention: Drug: Etravirine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
105
October 2012
October 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Male or female at least 18 years of age available for a follow-up period of at least 96 weeks.
  • HIV 1 RNA viral load of greater then 500 copies/mL.
  • Negative urine pregnancy test.

Exclusion Criteria:

  • Suspected or documented active, untreated HIV-1 related opportunistic infection or other condition requiring acute therapy at the time of randomization.
  • Subjects with acute Hepatitis B and/or C within 30 days of randomization.
  • Previous use of Darunavir or etravirine
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Brazil,   Germany,   Italy,   Malaysia,   Poland,   Portugal,   Puerto Rico,   South Africa,   Spain,   Taiwan,   Ukraine,   United Kingdom
 
NCT00823979
A5271022
Yes
Pfizer
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
March 2014

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