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

History of Changes

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
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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 ]

Show Outcome Measure 1

2. Secondary:

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

Show Outcome Measure 2

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 ]

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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 ]

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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 ]

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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 ]

Show Outcome Measure 6

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 ]

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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 ]

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Measure Type	Secondary
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
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 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
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 Cluster of Differentiation 4 (CD4+) Percentage Lymphocyte Counts at Week 24, 48, 96 [units: percentage of total lymphocytes] Mean ± Standard Deviation
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 ]

Show Outcome Measure 9

10. Secondary:

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

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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 ]

Show Outcome Measure 11

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

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Other Adverse Events

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

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

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