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
  Purpose

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.


Condition Intervention Phase
HIV-1
Drug: UK-453,061 Dose 1
Drug: UK-453,061 Dose 2
Drug: Etravirine
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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.


Enrollment: 105
Study Start Date: March 2009
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: UK- 453,061 Dose One Drug: UK-453,061 Dose 1
UK 453,061 750 mg QD + one optimized NRTI + darunavir/ritonavir.
Experimental: UK- 453,061 Dose Two Drug: UK-453,061 Dose 2
UK 453,061 1000 mg QD + one optimized NRTI + darunavir/ritonavir.
Active Comparator: Comparator Drug: Etravirine
Etravirine 200 mg BID + one optimized NRTI + darunavir/ritonavir.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00823979

  Show 63 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00823979     History of Changes
Other Study ID Numbers: A5271022
Study First Received: January 15, 2009
Results First Received: January 28, 2014
Last Updated: March 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
HIV-1 NNRTI Treatment Experienced
may have Protease inhibitor experience

Additional relevant MeSH terms:
Darunavir
Etravirine
Reverse Transcriptase Inhibitors
Ritonavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014