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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
Results First Received: January 28, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV-1
Interventions: Drug: UK-453,061 Dose 1
Drug: UK-453,061 Dose 2
Drug: Etravirine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Lersivirine 750 mg Lersivirine (UK-453,061) 250 milligram (mg) 3 tablets equivalent to lersivirine 750 mg and 1 placebo tablet matched to lersivirine 250 mg tablet, orally once daily up to 96 weeks in combination with 1 optimized nucleoside reverse transcriptase inhibitors (NRTI) as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily.
Lersivirine 1000 mg Lersivirine (UK-453,061) 250 mg 4 tablets equivalent to lersivirine 1000 mg, orally once daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily.
Etravirine 200 mg Etravirine 100 mg 2 tablets equivalent to etravirine 200 mg, orally twice daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily.

Participant Flow:   Overall Study
    Lersivirine 750 mg     Lersivirine 1000 mg     Etravirine 200 mg  
STARTED     35     35     35  
Treated     31     32     34  
COMPLETED     6     3     11  
NOT COMPLETED     29     32     24  
Lack of Efficacy                 13                 16                 9  
Lost to Follow-up                 2                 1                 0  
Withdrawal by Subject                 2                 3                 2  
Protocol Violation                 1                 1                 0  
Pregnancy                 0                 1                 0  
Adverse Event                 0                 2                 4  
Unspecified                 2                 0                 1  
Randomized but not Treated                 4                 3                 1  
Study Terminated by Sponsor                 5                 5                 7  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) population included all randomized participants who received at least 1 dose of study drug.

Reporting Groups
  Description
Lersivirine 750 mg Lersivirine (UK-453,061) 250 milligram (mg) 3 tablets equivalent to lersivirine 750 mg and 1 placebo tablet matched to lersivirine 250 mg tablet, orally once daily up to 96 weeks in combination with 1 optimized nucleoside reverse transcriptase inhibitors (NRTI) as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily.
Lersivirine 1000 mg Lersivirine (UK-453,061) 250 mg 4 tablets equivalent to lersivirine 1000 mg, orally once daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily.
Etravirine 200 mg Etravirine 100 mg 2 tablets equivalent to etravirine 200 mg, orally twice daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily.
Total Total of all reporting groups

Baseline Measures
    Lersivirine 750 mg     Lersivirine 1000 mg     Etravirine 200 mg     Total  
Number of Participants  
[units: participants]
  31     32     34     97  
Age  
[units: years]
Mean ± Standard Deviation
  41.1  ± 8.9     40.0  ± 8.7     41.9  ± 9.1     41.0  ± 8.9  
Gender  
[units: participants]
       
Female     15     18     18     51  
Male     16     14     16     46  



  Outcome Measures
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1.  Primary:   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 ]

2.  Secondary:   Percentage of Participants With HIV-1 RNA Levels <50 Copies/mL at Week 48 and 96   [ Time Frame: Weeks 48, 96 ]

3.  Secondary:   Percentage of Participants With HIV-1 RNA Levels <400 Copies/mL at Week 24, 48 and 96   [ Time Frame: Week 24, 48, 96 ]

4.  Secondary:   Change From Baseline in log10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96   [ Time Frame: Baseline, Week 24, 48, 96 ]
  Hide Outcome Measure 4

Measure Type Secondary
Measure Title Change From Baseline in log10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96
Measure Description 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 Frame Baseline, Week 24, 48, 96  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population. Participant discontinued before a visit of interest: value imputed as zero; not discontinued but observation is missing: last observation carried forward (LOCF) imputation used; missing baseline or no HIV-1 RNA level assessment: value imputed as zero.

Reporting Groups
  Description
Lersivirine 750 mg Lersivirine (UK-453,061) 250 milligram (mg) 3 tablets equivalent to lersivirine 750 mg and 1 placebo tablet matched to lersivirine 250 mg tablet, orally once daily up to 96 weeks in combination with 1 optimized nucleoside reverse transcriptase inhibitors (NRTI) as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily.
Lersivirine 1000 mg Lersivirine (UK-453,061) 250 mg 4 tablets equivalent to lersivirine 1000 mg, orally once daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily.
Etravirine 200 mg Etravirine 100 mg 2 tablets equivalent to etravirine 200 mg, orally twice daily up to 96 weeks in combination with 1 optimized NRTI as per individual prescribing information, darunavir 600 mg tablet orally twice daily and ritonavir 100 mg tablet or capsule orally twice daily.

Measured Values
    Lersivirine 750 mg     Lersivirine 1000 mg     Etravirine 200 mg  
Number of Participants Analyzed  
[units: participants]
  31     32     34  
Change From Baseline in log10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96  
[units: log10┬ácopies/mL]
Mean ± Standard Deviation
     
Baseline     4.28  ± 0.99     4.76  ± 0.82     4.59  ± 0.79  
Change at Week 24     -1.53  ± 1.58     -1.89  ± 1.46     -2.32  ± 1.21  
Change at Week 48     -1.30  ± 1.64     -1.08  ± 1.48     -2.06  ± 1.42  
Change at Week 96     -0.69  ± 1.39     -0.36  ± 1.00     -0.96  ± 1.49  

No statistical analysis provided for Change From Baseline in log10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96



5.  Secondary:   Time-Averaged Difference (TAD) in log10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96   [ Time Frame: Week 24, 48, 96 ]

6.  Secondary:   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 ]

7.  Secondary:   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 ]

8.  Secondary:   Change From Baseline in Cluster of Differentiation 4 (CD4+) Percentage Lymphocyte Counts at Week 24, 48, 96   [ Time Frame: Baseline, Week 24, 48, 96 ]

9.  Secondary:   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 ]

10.  Secondary:   Number of Participants With Laboratory Test Abnormalities   [ Time Frame: Baseline up to Week 48 or early termination ]

11.  Secondary:   Lersivirine Success Percentage With Reference to Median Minimum Observed Plasma Concentration (Cmin)   [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 ]

12.  Secondary:   Population Pharmacokinetics (PK) of Lersivirine   [ Time Frame: Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com


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