Trial Outcomes & Findings for 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 (NCT NCT00823979)

NCT ID: NCT00823979

Last Updated: 2018-12-04

Results Overview

Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

105 participants

Primary outcome timeframe

Week 24

Results posted on

2018-12-04

Participant Flow

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	35	35	35
Overall Study Treated	31	32	34
Overall Study COMPLETED	6	3	11
Overall Study NOT COMPLETED	29	32	24

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Lack of Efficacy	13	16	9
Overall Study Lost to Follow-up	2	1	0
Overall Study Withdrawal by Subject	2	3	2
Overall Study Protocol Violation	1	1	0
Overall Study Pregnancy	0	1	0
Overall Study Adverse Event	0	2	4
Overall Study Other	2	0	1
Overall Study Randomized but not Treated	4	3	1
Overall Study Study Terminated by Sponsor	5	5	7

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lersivirine 750 mg n=31 Participants 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 n=32 Participants 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 n=34 Participants 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 n=97 Participants Total of all reporting groups
Age, Continuous	41.1 years STANDARD_DEVIATION 8.9 • n=5 Participants	40.0 years STANDARD_DEVIATION 8.7 • n=7 Participants	41.9 years STANDARD_DEVIATION 9.1 • n=5 Participants	41.0 years STANDARD_DEVIATION 8.9 • n=4 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	18 Participants n=7 Participants	18 Participants n=5 Participants	51 Participants n=4 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	14 Participants n=7 Participants	16 Participants n=5 Participants	46 Participants n=4 Participants

PRIMARY outcome

Timeframe: Week 24

Population: ITT population. Participants who died, discontinued, lost to follow-up, switched/changed dose of anti-retro viral (ARV) drug not allowed by protocol, had missing plasma HIV-1 RNA data at 24 weeks were considered to have plasma HIV-1 RNA \>=50 copies/mL and were referred to as failure.

Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5).

Outcome measures

Outcome measures
Measure	Lersivirine 750 mg n=31 Participants 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 n=32 Participants 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 n=34 Participants 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.
Percentage of Participants With Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) Levels Less Than (<) 50 Copies/Milliliter (mL) at Week 24	48.4 percentage of participants	43.8 percentage of participants	67.6 percentage of participants

SECONDARY outcome

Timeframe: Weeks 48, 96

Population: ITT population. Participants who died, discontinued,lost to follow-up,switched/changed dose of ARV drug not allowed by protocol,had missing plasma HIV-1 RNA data at 48, 96 weeks were considered to have plasma HIV-1 RNA \>=50 copies/mL and were referred to as failure. n=participants evaluable at specified time point for each arm group, respectively.

Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5).

Outcome measures

Outcome measures
Measure	Lersivirine 750 mg n=31 Participants 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 n=32 Participants 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 n=34 Participants 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.
Percentage of Participants With HIV-1 RNA Levels <50 Copies/mL at Week 48 and 96 Week 48 (n=31, 32, 34)	41.9 percentage of participants	31.3 percentage of participants	61.8 percentage of participants
Percentage of Participants With HIV-1 RNA Levels <50 Copies/mL at Week 48 and 96 Week 96 (n=28, 28, 27)	25.0 percentage of participants	14.3 percentage of participants	37.0 percentage of participants

SECONDARY outcome

Timeframe: Week 24, 48, 96

Population: ITT population. Participants who died,discontinued,lost to follow-up,switched/changed dose of ARV drug not allowed by protocol,had missing plasma HIV-1 RNA data at 24, 48, 96 weeks were considered to have plasma HIV-1 RNA \>=400 copies/mL and referred to as failure. n=participants evaluable at specified time point for each arm group, respectively.

Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5).

Outcome measures

Outcome measures
Measure	Lersivirine 750 mg n=31 Participants 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 n=32 Participants 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 n=34 Participants 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.
Percentage of Participants With HIV-1 RNA Levels <400 Copies/mL at Week 24, 48 and 96 Week 24 (n=31, 32, 34)	54.8 percentage of participants	50.0 percentage of participants	79.4 percentage of participants
Percentage of Participants With HIV-1 RNA Levels <400 Copies/mL at Week 24, 48 and 96 Week 48 (n=31, 32, 34)	41.9 percentage of participants	34.4 percentage of participants	70.6 percentage of participants
Percentage of Participants With HIV-1 RNA Levels <400 Copies/mL at Week 24, 48 and 96 Week 96 (n=28, 28, 27)	25.0 percentage of participants	14.3 percentage of participants	37.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 24, 48, 96

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Lersivirine 750 mg n=31 Participants 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 n=32 Participants 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 n=34 Participants 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.
Change From Baseline in log10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96 Baseline	4.28 log10 copies/mL Standard Deviation 0.99	4.76 log10 copies/mL Standard Deviation 0.82	4.59 log10 copies/mL Standard Deviation 0.79
Change From Baseline in log10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96 Change at Week 24	-1.53 log10 copies/mL Standard Deviation 1.58	-1.89 log10 copies/mL Standard Deviation 1.46	-2.32 log10 copies/mL Standard Deviation 1.21
Change From Baseline in log10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96 Change at Week 48	-1.30 log10 copies/mL Standard Deviation 1.64	-1.08 log10 copies/mL Standard Deviation 1.48	-2.06 log10 copies/mL Standard Deviation 1.42
Change From Baseline in log10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96 Change at Week 96	-0.69 log10 copies/mL Standard Deviation 1.39	-0.36 log10 copies/mL Standard Deviation 1.00	-0.96 log10 copies/mL Standard Deviation 1.49

SECONDARY outcome

Timeframe: Week 24, 48, 96

Population: ITT population. Participant discontinued before a visit of interest: TAD imputed as zero; not discontinued but observation was missing at visit: TAD to the last non-missing timepoint; not discontinued and missing values between baseline and visit: ignore missing values; missing baseline or no HIV-1 RNA level assessment: TAD imputed as zero.

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.

Outcome measures

Outcome measures
Measure	Lersivirine 750 mg n=31 Participants 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 n=32 Participants 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 n=34 Participants 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.
Time-Averaged Difference (TAD) in log10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96 Week 24	-1.46 log10 copies/mL Standard Deviation 1.12	-1.72 log10 copies/mL Standard Deviation 1.11	-2.10 log10 copies/mL Standard Deviation 0.92
Time-Averaged Difference (TAD) in log10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96 Week 48	-1.28 log10 copies/mL Standard Deviation 1.39	-1.19 log10 copies/mL Standard Deviation 1.35	-1.89 log10 copies/mL Standard Deviation 1.27

SECONDARY outcome

Timeframe: Week 24, 48, 96

Population: ITT.Participants who died,discontinued,lost to follow-up,switched/changed dose of ARV drug not allowed by protocol,had missing plasma HIV-1 RNA data at 24,48 weeks were considered to have plasma HIV-1 RNA\>=50 copies/mL;were referred as failure. Due to early termination of study,decision was made not to derive TLOVR50 responder analysis for Week 96.

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.

Outcome measures

Outcome measures
Measure	Lersivirine 750 mg n=31 Participants 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 n=32 Participants 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 n=34 Participants 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.
Percentage of Participants With Response as Determined by the Time to Loss of Virologic Response (TLOVR50) Algorithm at Week 24, 48 and 96 Week 24	48.4 percentage of participants	43.8 percentage of participants	67.6 percentage of participants
Percentage of Participants With Response as Determined by the Time to Loss of Virologic Response (TLOVR50) Algorithm at Week 24, 48 and 96 Week 48	41.9 percentage of participants	28.1 percentage of participants	55.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 24, 48, 96

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Lersivirine 750 mg n=31 Participants 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 n=32 Participants 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 n=34 Participants 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.
Change From Baseline in Cluster of Differentiation 4 (CD4+) Absolute Lymphocyte Counts at Week 24, 48 and 96 Baseline	247 cells per microliter (cells/mcL) Standard Deviation 143	259 cells per microliter (cells/mcL) Standard Deviation 187	227 cells per microliter (cells/mcL) Standard Deviation 146
Change From Baseline in Cluster of Differentiation 4 (CD4+) Absolute Lymphocyte Counts at Week 24, 48 and 96 Change at Week 24	98 cells per microliter (cells/mcL) Standard Deviation 140	66 cells per microliter (cells/mcL) Standard Deviation 111	110 cells per microliter (cells/mcL) Standard Deviation 108
Change From Baseline in Cluster of Differentiation 4 (CD4+) Absolute Lymphocyte Counts at Week 24, 48 and 96 Change at Week 48	122 cells per microliter (cells/mcL) Standard Deviation 148	74 cells per microliter (cells/mcL) Standard Deviation 128	128 cells per microliter (cells/mcL) Standard Deviation 127
Change From Baseline in Cluster of Differentiation 4 (CD4+) Absolute Lymphocyte Counts at Week 24, 48 and 96 Change at Week 96	148 cells per microliter (cells/mcL) Standard Deviation 177	89 cells per microliter (cells/mcL) Standard Deviation 152	184 cells per microliter (cells/mcL) Standard Deviation 197

SECONDARY outcome

Timeframe: Baseline, Week 24, 48, 96

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.

Outcome measures

Outcome measures
Measure	Lersivirine 750 mg n=31 Participants 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 n=32 Participants 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 n=34 Participants 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.
Change From Baseline in Cluster of Differentiation 4 (CD4+) Percentage Lymphocyte Counts at Week 24, 48, 96 Change at Week 96	5.4 percentage of total lymphocytes Standard Deviation 6.1	4.2 percentage of total lymphocytes Standard Deviation 4.9	6.2 percentage of total lymphocytes Standard Deviation 6.2
Change From Baseline in Cluster of Differentiation 4 (CD4+) Percentage Lymphocyte Counts at Week 24, 48, 96 Baseline	16.1 percentage of total lymphocytes Standard Deviation 8.7	15.0 percentage of total lymphocytes Standard Deviation 8.8	14.6 percentage of total lymphocytes Standard Deviation 8.3
Change From Baseline in Cluster of Differentiation 4 (CD4+) Percentage Lymphocyte Counts at Week 24, 48, 96 Change at Week 24	3.0 percentage of total lymphocytes Standard Deviation 4.0	3.7 percentage of total lymphocytes Standard Deviation 3.6	3.7 percentage of total lymphocytes Standard Deviation 3.2
Change From Baseline in Cluster of Differentiation 4 (CD4+) Percentage Lymphocyte Counts at Week 24, 48, 96 Change at Week 48	4.6 percentage of total lymphocytes Standard Deviation 5.3	4.0 percentage of total lymphocytes Standard Deviation 4.1	4.4 percentage of total lymphocytes Standard Deviation 3.8

SECONDARY outcome

Timeframe: Baseline through Week 48

Population: Virology analysis set included a subset of participants from TLOVR50 failures who had valid genotypic or phenotypic susceptibility testing result and with plasma HIV-1 RNA \>500 copies/mL at baseline and treatment failure.

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.

Outcome measures

Outcome measures
Measure	Lersivirine 750 mg n=12 Participants 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 n=16 Participants 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 n=4 Participants 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.
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	5 participants	3 participants	1 participants

SECONDARY outcome

Timeframe: Baseline up to Week 48 or early termination

Population: Safety analysis set included all randomized participants who received at least 1 dose of study medication. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Laboratory analysis included blood chemistry, hematology and urinalysis.

Outcome measures

Outcome measures
Measure	Lersivirine 750 mg n=29 Participants 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 n=31 Participants 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 n=34 Participants 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.
Number of Participants With Laboratory Test Abnormalities	27 participants	30 participants	33 participants

SECONDARY outcome

Timeframe: Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48

Population: Due to the sparsity of the data, the ability to interpret the pharmacokinetic/pharmacodynamic (PK/PD) results was limited, thus the data was not reported.

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.

Outcome measures

Outcome data not reported

Adverse Events

Lersivirine 750 mg

Serious events: 1 serious events

Other events: 27 other events

Deaths: 0 deaths

Lersivirine 1000 mg

Serious events: 4 serious events

Other events: 25 other events

Deaths: 0 deaths

Etravirine 200 mg

Serious events: 1 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Lersivirine 750 mg n=31 participants at risk 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 n=32 participants at risk 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 n=34 participants at risk 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.
Cardiac disorders Coronary artery disease	0.00% 0/31 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.1% 1/32 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Pneumocystis jiroveci pneumonia	0.00% 0/31 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/32 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Pneumonia	0.00% 0/31 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/32 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Pulmonary tuberculosis	0.00% 0/31 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.2% 2/32 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Head injury	0.00% 0/31 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.1% 1/32 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Vascular disorders Hypertension	3.2% 1/31 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/32 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Other adverse events

Additional Information

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Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER