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
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT00823979 |
Recruitment Status
:
Terminated
(See termination reason in detailed description.)
First Posted
: January 16, 2009
Results First Posted
: March 14, 2014
Last Update Posted
: April 16, 2014
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Sponsor:
Pfizer
Information provided by (Responsible Party):
Pfizer
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Study Type: | Interventional |
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Study Design: | Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment |
Condition: |
HIV-1 |
Interventions: |
Drug: UK-453,061 Dose 1 Drug: UK-453,061 Dose 2 Drug: Etravirine |

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations |
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No text entered. |
Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment |
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No text entered. |
Reporting Groups
Description | |
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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 | |
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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 |
Other | 2 | 0 | 1 |
Randomized but not Treated | 4 | 3 | 1 |
Study Terminated by Sponsor | 5 | 5 | 7 |

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. |
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Intent-to-Treat (ITT) population included all randomized participants who received at least 1 dose of study drug. |
Reporting Groups
Description | |
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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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Overall Participants Analyzed [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] |
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Female | 15 | 18 | 18 | 51 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Male | 16 | 14 | 16 | 46 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||

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 ] |
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 ] |

Measure Type | Secondary |
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Measure Title | Change From Baseline in Cluster of Differentiation 4 (CD4+) Percentage Lymphocyte Counts at Week 24, 48, 96 |
Measure Description | 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. |
Time Frame | Baseline, Week 24, 48, 96 |
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. |
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ITT population included all randomized participants who received at least 1 dose of study drug. Missing values were imputed using LOCF. Participants with missing baseline or no CD4+ count available on treatment imputed as no or zero change from baseline. |
Reporting Groups
Description | |
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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 | |
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Participants Analyzed [Units: Participants] |
31 | 32 | 34 |
Change From Baseline in Cluster of Differentiation 4 (CD4+) Percentage Lymphocyte Counts at Week 24, 48, 96 [Units: Percentage of total lymphocytes] Mean (Standard Deviation) |
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Baseline | 16.1 (8.7) | 15.0 (8.8) | 14.6 (8.3) |
Change at Week 24 | 3.0 (4.0) | 3.7 (3.6) | 3.7 (3.2) |
Change at Week 48 | 4.6 (5.3) | 4.0 (4.1) | 4.4 (3.8) |
Change at Week 96 | 5.4 (6.1) | 4.2 (4.9) | 6.2 (6.2) |
No statistical analysis provided for Change From Baseline in Cluster of Differentiation 4 (CD4+) Percentage Lymphocyte Counts at 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.

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 |
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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. |

Certain Agreements:
Results Point of Contact:
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:
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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
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com
Responsible Party: | Pfizer |
ClinicalTrials.gov Identifier: | NCT00823979 History of Changes |
Other Study ID Numbers: |
A5271022 |
First Submitted: | January 15, 2009 |
First Posted: | January 16, 2009 |
Results First Submitted: | January 28, 2014 |
Results First Posted: | March 14, 2014 |
Last Update Posted: | April 16, 2014 |