A Study Of Different Doses Of UK-453, 061 Plus Truvada Compared To Efavirenz Plus Truvada In Patients Who Have Not Been Previously Treated For HIV-1

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00824421
First received: January 15, 2009
Last updated: December 9, 2013
Last verified: November 2011
Results First Received: December 9, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: HIV-1
Interventions: Drug: UK-453, 061
Drug: EFV +TVA

  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 500 mg Two lersivirine 250 milligram (mg) tablets (equivalent to lersivirine 500 mg), a placebo tablet matched to lersivirine and a placebo tablet matched to efavirenz orally once daily along with tenofovir disoproxil fumarate (DF) 300 mg tablet and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in pharmacokinetic (PK) substudy switched to lersivirine morning dosing regimen, received 2 Lersivirine 250 mg tablets, a placebo tablet matched to lersivirine orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.
Lersivirine 750 mg Three Lersivirine 250 mg tablets (equivalent to lersivirine 750 mg) and a placebo tablet matched to efavirenz orally once daily along with tenofovir DF 300 mg and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in PK substudy switched to morning dosing regimen, received 3 Lersivirine 250 mg tablets orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.
Efavirenz 600 mg Three placebo tablets matched to lersivirine, efavirenz 600 mg tablet orally once daily along with tenofovir DF 300 mg and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in PK substudy switched to morning dosing regimen, received 3 placebo tablets matched to lersivirine and efavirenz 600 mg tablet orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. Efavirenz 600 mg tablet, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.

Participant Flow:   Overall Study
    Lersivirine 500 mg     Lersivirine 750 mg     Efavirenz 600 mg  
STARTED     66     66     63  
Treated     65     65     63  
COMPLETED     49     44     49  
NOT COMPLETED     17     22     14  
Adverse Event                 6                 6                 6  
Death                 0                 1                 0  
Lack of Efficacy                 5                 7                 4  
Lost to Follow-up                 2                 3                 0  
Pregnancy                 1                 0                 1  
Withdrawal by Subject                 2                 3                 3  
Randomized but not Treated                 1                 1                 0  
Unspecified                 0                 1                 0  



  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 had received at least 1 dose of study medication.

Reporting Groups
  Description
Lersivirine 500 mg Two lersivirine 250 milligram (mg) tablets (equivalent to lersivirine 500 mg), a placebo tablet matched to lersivirine and a placebo tablet matched to efavirenz orally once daily along with tenofovir disoproxil fumarate (DF) 300 mg tablet and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in pharmacokinetic (PK) substudy switched to lersivirine morning dosing regimen, received 2 Lersivirine 250 mg tablets, a placebo tablet matched to lersivirine orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.
Lersivirine 750 mg Three Lersivirine 250 mg tablets (equivalent to lersivirine 750 mg) and a placebo tablet matched to efavirenz orally once daily along with tenofovir DF 300 mg and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in PK substudy switched to morning dosing regimen, received 3 Lersivirine 250 mg tablets orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.
Efavirenz 600 mg Three placebo tablets matched to lersivirine, efavirenz 600 mg tablet orally once daily along with tenofovir DF 300 mg and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in PK substudy switched to morning dosing regimen, received 3 placebo tablets matched to lersivirine and efavirenz 600 mg tablet orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. Efavirenz 600 mg tablet, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.
Total Total of all reporting groups

Baseline Measures
    Lersivirine 500 mg     Lersivirine 750 mg     Efavirenz 600 mg     Total  
Number of Participants  
[units: participants]
  65     65     63     193  
Age  
[units: years]
Mean ± Standard Deviation
  36.5  ± 8.0     35.7  ± 8.2     36.3  ± 8.7     36.2  ± 8.2  
Gender  
[units: participants]
       
Female     16     19     17     52  
Male     49     46     46     141  



  Outcome Measures
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1.  Primary:   Percentage of Participants With Less Than 50 Copies Per Milliliter (Copies/mL) of Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) at Week 48   [ Time Frame: Week 48 ]

Measure Type Primary
Measure Title Percentage of Participants With Less Than 50 Copies Per Milliliter (Copies/mL) of Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) at Week 48
Measure Description Plasma HIV-1 RNA level was determined by validated Roche Amplicor HIV-1 Monitor standard assay.
Time Frame Week 48  
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 medication. Participants who had been discontinued from the study, were lost to follow-up, or had missing HIV-1 RNA level data at a visit were considered to have HIV-1 RNA levels >=50 copies/mL and were referred to as non-completer = failure.

Reporting Groups
  Description
Lersivirine 500 mg Two lersivirine 250 milligram (mg) tablets (equivalent to lersivirine 500 mg), a placebo tablet matched to lersivirine and a placebo tablet matched to efavirenz orally once daily along with tenofovir disoproxil fumarate (DF) 300 mg tablet and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in pharmacokinetic (PK) substudy switched to lersivirine morning dosing regimen, received 2 Lersivirine 250 mg tablets, a placebo tablet matched to lersivirine orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.
Lersivirine 750 mg Three Lersivirine 250 mg tablets (equivalent to lersivirine 750 mg) and a placebo tablet matched to efavirenz orally once daily along with tenofovir DF 300 mg and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in PK substudy switched to morning dosing regimen, received 3 Lersivirine 250 mg tablets orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.
Efavirenz 600 mg Three placebo tablets matched to lersivirine, efavirenz 600 mg tablet orally once daily along with tenofovir DF 300 mg and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in PK substudy switched to morning dosing regimen, received 3 placebo tablets matched to lersivirine and efavirenz 600 mg tablet orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. Efavirenz 600 mg tablet, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.

Measured Values
    Lersivirine 500 mg     Lersivirine 750 mg     Efavirenz 600 mg  
Number of Participants Analyzed  
[units: participants]
  65     65     63  
Percentage of Participants With Less Than 50 Copies Per Milliliter (Copies/mL) of Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) at Week 48  
[units: percentage of participants]
  78.5     78.5     85.7  

No statistical analysis provided for Percentage of Participants With Less Than 50 Copies Per Milliliter (Copies/mL) of Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) at Week 48



2.  Secondary:   Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA at Week 24 and 96   [ Time Frame: Week 24, 96 ]

Measure Type Secondary
Measure Title Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA at Week 24 and 96
Measure Description Plasma HIV-1 RNA level was determined by validated Roche Amplicor HIV-1 Monitor standard assay.
Time Frame Week 24, 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 medication. Participants who had been discontinued from the study, were lost to follow-up, or had missing HIV-1 RNA level data at a visit were considered to have HIV-1 RNA levels >=50 copies/mL and were referred to as non-completer = failure.

Reporting Groups
  Description
Lersivirine 500 mg Two lersivirine 250 milligram (mg) tablets (equivalent to lersivirine 500 mg), a placebo tablet matched to lersivirine and a placebo tablet matched to efavirenz orally once daily along with tenofovir disoproxil fumarate (DF) 300 mg tablet and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in pharmacokinetic (PK) substudy switched to lersivirine morning dosing regimen, received 2 Lersivirine 250 mg tablets, a placebo tablet matched to lersivirine orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.
Lersivirine 750 mg Three Lersivirine 250 mg tablets (equivalent to lersivirine 750 mg) and a placebo tablet matched to efavirenz orally once daily along with tenofovir DF 300 mg and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in PK substudy switched to morning dosing regimen, received 3 Lersivirine 250 mg tablets orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.
Efavirenz 600 mg Three placebo tablets matched to lersivirine, efavirenz 600 mg tablet orally once daily along with tenofovir DF 300 mg and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in PK substudy switched to morning dosing regimen, received 3 placebo tablets matched to lersivirine and efavirenz 600 mg tablet orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. Efavirenz 600 mg tablet, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.

Measured Values
    Lersivirine 500 mg     Lersivirine 750 mg     Efavirenz 600 mg  
Number of Participants Analyzed  
[units: participants]
  65     65     63  
Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA at Week 24 and 96  
[units: percentage of participants]
     
Week 24     83.1     83.1     87.3  
Week 96     70.8     67.7     77.8  

No statistical analysis provided for Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA at Week 24 and 96



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

Measure Type Secondary
Measure Title Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA at Week 24, 48 and 96
Measure Description Plasma HIV-1 RNA level was determined by validated Roche Amplicor HIV-1 Monitor standard assay.
Time Frame 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 medication. Participants who had been discontinued from the study, were lost to follow-up, or had missing HIV-1 RNA level data at a visit were considered to have HIV-1 RNA levels >=400 copies/mL and were referred to as non-completer = failure.

Reporting Groups
  Description
Lersivirine 500 mg Two lersivirine 250 milligram (mg) tablets (equivalent to lersivirine 500 mg), a placebo tablet matched to lersivirine and a placebo tablet matched to efavirenz orally once daily along with tenofovir disoproxil fumarate (DF) 300 mg tablet and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in pharmacokinetic (PK) substudy switched to lersivirine morning dosing regimen, received 2 Lersivirine 250 mg tablets, a placebo tablet matched to lersivirine orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.
Lersivirine 750 mg Three Lersivirine 250 mg tablets (equivalent to lersivirine 750 mg) and a placebo tablet matched to efavirenz orally once daily along with tenofovir DF 300 mg and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in PK substudy switched to morning dosing regimen, received 3 Lersivirine 250 mg tablets orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.
Efavirenz 600 mg Three placebo tablets matched to lersivirine, efavirenz 600 mg tablet orally once daily along with tenofovir DF 300 mg and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in PK substudy switched to morning dosing regimen, received 3 placebo tablets matched to lersivirine and efavirenz 600 mg tablet orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. Efavirenz 600 mg tablet, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.

Measured Values
    Lersivirine 500 mg     Lersivirine 750 mg     Efavirenz 600 mg  
Number of Participants Analyzed  
[units: participants]
  65     65     63  
Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA at Week 24, 48 and 96  
[units: percentage of participants]
     
Week 24     84.6     87.7     90.5  
Week 48     81.5     80.0     85.7  
Week 96     73.8     67.7     77.8  

No statistical analysis provided for Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA at Week 24, 48 and 96



4.  Secondary:   Change From Baseline in Log 10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96   [ Time Frame: Baseline, Week 24, 48, 96 ]

Measure Type Secondary
Measure Title Change From Baseline in Log 10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96
Measure Description For the log 10 scale, all the HIV-1 RNA levels were log 10 transformed prior to the average calculations. Baseline value was calculated as the average of all 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. 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 500 mg Two lersivirine 250 milligram (mg) tablets (equivalent to lersivirine 500 mg), a placebo tablet matched to lersivirine and a placebo tablet matched to efavirenz orally once daily along with tenofovir disoproxil fumarate (DF) 300 mg tablet and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in pharmacokinetic (PK) substudy switched to lersivirine morning dosing regimen, received 2 Lersivirine 250 mg tablets, a placebo tablet matched to lersivirine orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.
Lersivirine 750 mg Three Lersivirine 250 mg tablets (equivalent to lersivirine 750 mg) and a placebo tablet matched to efavirenz orally once daily along with tenofovir DF 300 mg and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in PK substudy switched to morning dosing regimen, received 3 Lersivirine 250 mg tablets orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.
Efavirenz 600 mg Three placebo tablets matched to lersivirine, efavirenz 600 mg tablet orally once daily along with tenofovir DF 300 mg and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in PK substudy switched to morning dosing regimen, received 3 placebo tablets matched to lersivirine and efavirenz 600 mg tablet orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. Efavirenz 600 mg tablet, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.

Measured Values
    Lersivirine 500 mg     Lersivirine 750 mg     Efavirenz 600 mg  
Number of Participants Analyzed  
[units: participants]
  65     65     63  
Change From Baseline in Log 10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96  
[units: log 10 copies/mL]
Mean ± Standard Deviation
     
Baseline     4.62  ± 0.61     4.69  ± 0.66     4.66  ± 0.62  
Change at Week 24     -2.44  ± 1.19     -2.63  ± 1.11     -2.68  ± 1.05  
Change at Week 48     -2.36  ± 1.26     -2.34  ± 1.33     -2.52  ± 1.17  
Change at Week 96     -2.19  ± 1.38     -1.98  ± 1.48     -2.27  ± 1.34  

No statistical analysis provided for Change From Baseline in Log 10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96



5.  Secondary:   Time-Averaged Difference (TAD) in Log 10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96   [ Time Frame: Baseline up to Week 24, 48, 96 ]

Measure Type Secondary
Measure Title Time-Averaged Difference (TAD) in Log 10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96
Measure Description 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 was calculated as the average of all the measurements collected prior to and including Day 1 pre-dose.
Time Frame Baseline up to 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 was missing: value calculated 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: value imputed as zero.

Reporting Groups
  Description
Lersivirine 500 mg Two lersivirine 250 milligram (mg) tablets (equivalent to lersivirine 500 mg), a placebo tablet matched to lersivirine and a placebo tablet matched to efavirenz orally once daily along with tenofovir disoproxil fumarate (DF) 300 mg tablet and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in pharmacokinetic (PK) substudy switched to lersivirine morning dosing regimen, received 2 Lersivirine 250 mg tablets, a placebo tablet matched to lersivirine orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.
Lersivirine 750 mg Three Lersivirine 250 mg tablets (equivalent to lersivirine 750 mg) and a placebo tablet matched to efavirenz orally once daily along with tenofovir DF 300 mg and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in PK substudy switched to morning dosing regimen, received 3 Lersivirine 250 mg tablets orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.
Efavirenz 600 mg Three placebo tablets matched to lersivirine, efavirenz 600 mg tablet orally once daily along with tenofovir DF 300 mg and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in PK substudy switched to morning dosing regimen, received 3 placebo tablets matched to lersivirine and efavirenz 600 mg tablet orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. Efavirenz 600 mg tablet, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.

Measured Values
    Lersivirine 500 mg     Lersivirine 750 mg     Efavirenz 600 mg  
Number of Participants Analyzed  
[units: participants]
  65     65     63  
Time-Averaged Difference (TAD) in Log 10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96  
[units: log10 copies/mL]
Mean ± Standard Deviation
     
Week 24     -2.17  ± 0.99     -2.30  ± 0.94     -2.40  ± 0.89  
Week 48     -2.23  ± 1.17     -2.24  ± 1.19     -2.39  ± 1.09  
Week 96     -2.16  ± 1.33     -1.92  ± 1.43     -2.21  ± 1.29  

No statistical analysis provided for Time-Averaged Difference (TAD) in Log 10 Transformed HIV-1 RNA Levels at Week 24, 48 and 96



6.  Secondary:   Percentage of Participants With Response as Determined Using the Time-to Loss of Virologic Response (TLOVR50) Algorithm at Week 24, 48 and 96   [ Time Frame: Week 24, 48, 96 ]

Measure Type Secondary
Measure Title Percentage of Participants With Response as Determined Using the Time-to Loss of Virologic Response (TLOVR50) Algorithm at Week 24, 48 and 96
Measure Description TLOVR50 response is 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; met treatment failure [TF] criteria). TF: an increase to at least 3 times 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). TF criteria’s defined above were confirmed by second measurement at least 14 days after first. In 'TLOVR50', '50' denotes the lower limit of quantification (LLOQ) of assay (which is 50 copies/mL). Baseline value was calculated as the average of all the measurements collected prior to and including Day 1 pre-dose.
Time Frame 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 medication. Missing value was imputed per the TLOVR algorithm.

Reporting Groups
  Description
Lersivirine 500 mg Two lersivirine 250 milligram (mg) tablets (equivalent to lersivirine 500 mg), a placebo tablet matched to lersivirine and a placebo tablet matched to efavirenz orally once daily along with tenofovir disoproxil fumarate (DF) 300 mg tablet and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in pharmacokinetic (PK) substudy switched to lersivirine morning dosing regimen, received 2 Lersivirine 250 mg tablets, a placebo tablet matched to lersivirine orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.
Lersivirine 750 mg Three Lersivirine 250 mg tablets (equivalent to lersivirine 750 mg) and a placebo tablet matched to efavirenz orally once daily along with tenofovir DF 300 mg and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in PK substudy switched to morning dosing regimen, received 3 Lersivirine 250 mg tablets orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.
Efavirenz 600 mg Three placebo tablets matched to lersivirine, efavirenz 600 mg tablet orally once daily along with tenofovir DF 300 mg and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in PK substudy switched to morning dosing regimen, received 3 placebo tablets matched to lersivirine and efavirenz 600 mg tablet orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. Efavirenz 600 mg tablet, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.

Measured Values
    Lersivirine 500 mg     Lersivirine 750 mg     Efavirenz 600 mg  
Number of Participants Analyzed  
[units: participants]
  65     65     63  
Percentage of Participants With Response as Determined Using the Time-to Loss of Virologic Response (TLOVR50) Algorithm at Week 24, 48 and 96  
[units: percentage of participants]
     
Week 24     83.1     83.1     87.3  
Week 48     78.5     78.5     85.7  
Week 96     67.7     67.7     76.2  

No statistical analysis provided for Percentage of Participants With Response as Determined Using the Time-to Loss of Virologic Response (TLOVR50) Algorithm at Week 24, 48 and 96



7.  Secondary:   Change From Baseline in Cluster of Differentiation (CD4+) Absolute Cell Count at Week 24, 48 and 96   [ Time Frame: Baseline, Week 24, 48, 96 ]

Measure Type Secondary
Measure Title Change From Baseline in Cluster of Differentiation (CD4+) Absolute Cell Count at Week 24, 48 and 96
Measure Description Baseline value was calculated as the average of all 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 medication. LOCF method was used to impute missing values. No or zero change from baseline was imputed for participants with missing baseline or no CD4+ count available on treatment.

Reporting Groups
  Description
Lersivirine 500 mg Two lersivirine 250 milligram (mg) tablets (equivalent to lersivirine 500 mg), a placebo tablet matched to lersivirine and a placebo tablet matched to efavirenz orally once daily along with tenofovir disoproxil fumarate (DF) 300 mg tablet and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in pharmacokinetic (PK) substudy switched to lersivirine morning dosing regimen, received 2 Lersivirine 250 mg tablets, a placebo tablet matched to lersivirine orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.
Lersivirine 750 mg Three Lersivirine 250 mg tablets (equivalent to lersivirine 750 mg) and a placebo tablet matched to efavirenz orally once daily along with tenofovir DF 300 mg and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in PK substudy switched to morning dosing regimen, received 3 Lersivirine 250 mg tablets orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.
Efavirenz 600 mg Three placebo tablets matched to lersivirine, efavirenz 600 mg tablet orally once daily along with tenofovir DF 300 mg and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in PK substudy switched to morning dosing regimen, received 3 placebo tablets matched to lersivirine and efavirenz 600 mg tablet orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. Efavirenz 600 mg tablet, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.

Measured Values
    Lersivirine 500 mg     Lersivirine 750 mg     Efavirenz 600 mg  
Number of Participants Analyzed  
[units: participants]
  65     65     63  
Change From Baseline in Cluster of Differentiation (CD4+) Absolute Cell Count at Week 24, 48 and 96  
[units: cells per microliter (cells/mcL)]
Mean ± Standard Deviation
     
Baseline     349  ± 120     352  ± 154     319  ± 80  
Change at Week 24     146  ± 164     167  ± 127     139  ± 104  
Change at Week 48     191  ± 206     195  ± 130     188  ± 117  
Change at Week 96     215  ± 194     231  ± 187     221  ± 144  

No statistical analysis provided for Change From Baseline in Cluster of Differentiation (CD4+) Absolute Cell Count at Week 24, 48 and 96



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

Measure Type Secondary
Measure Title Change From Baseline in Cluster of Differentiation (CD4+) Percentage Cell Count at Week 24, 48 and 96
Measure Description Baseline value was calculated as the average of all 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 medication. LOCF method was used to impute missing values. No or zero change from baseline was imputed for participants with missing baseline or no CD4+ count available on treatment.

Reporting Groups
  Description
Lersivirine 500 mg Two lersivirine 250 milligram (mg) tablets (equivalent to lersivirine 500 mg), a placebo tablet matched to lersivirine and a placebo tablet matched to efavirenz orally once daily along with tenofovir disoproxil fumarate (DF) 300 mg tablet and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in pharmacokinetic (PK) substudy switched to lersivirine morning dosing regimen, received 2 Lersivirine 250 mg tablets, a placebo tablet matched to lersivirine orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.
Lersivirine 750 mg Three Lersivirine 250 mg tablets (equivalent to lersivirine 750 mg) and a placebo tablet matched to efavirenz orally once daily along with tenofovir DF 300 mg and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in PK substudy switched to morning dosing regimen, received 3 Lersivirine 250 mg tablets orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.
Efavirenz 600 mg Three placebo tablets matched to lersivirine, efavirenz 600 mg tablet orally once daily along with tenofovir DF 300 mg and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in PK substudy switched to morning dosing regimen, received 3 placebo tablets matched to lersivirine and efavirenz 600 mg tablet orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. Efavirenz 600 mg tablet, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.

Measured Values
    Lersivirine 500 mg     Lersivirine 750 mg     Efavirenz 600 mg  
Number of Participants Analyzed  
[units: participants]
  65     65     63  
Change From Baseline in Cluster of Differentiation (CD4+) Percentage Cell Count at Week 24, 48 and 96  
[units: percentage of total lymphocytes]
Mean ± Standard Deviation
     
Baseline     19.9  ± 6.6     20.0  ± 6.7     19.5  ± 5.4  
Change at Week 24     6.0  ± 4.1     7.5  ± 3.7     7.3  ± 4.7  
Change at Week 48     8.3  ± 5.0     9.9  ± 4.3     8.7  ± 4.9  
Change at Week 96     10.1  ± 6.4     12.1  ± 6.5     11.1  ± 6.0  

No statistical analysis provided for Change From Baseline in Cluster of Differentiation (CD4+) Percentage Cell Count at Week 24, 48 and 96



9.  Secondary:   Number of Participants With NRTI and NNRTI Resistance-Associated Mutations (RAMs) at Time of Treatment Failure Through Week 24, 48 and 96   [ Time Frame: Day 1 (pre-dose) through Week 24, 48, 96 ]

Measure Type Secondary
Measure Title Number of Participants With NRTI and NNRTI Resistance-Associated Mutations (RAMs) at Time of Treatment Failure Through Week 24, 48 and 96
Measure Description Phenotypic resistance and genotypic resistance was assessed for all participants at Day 1 predose, and was evaluated for nucleotide reverse transcriptase inhibitors (NRTIs), and non-NRTIs (NNRTIs) resistance-associated mutations at time of treatment failure using Monogram GenoSeq and/or PhenoSenseGT assays. This was then repeated for all participants with HIV-1 viral load more than 500 copies/mL at treatment failure, up to Week 96.
Time Frame Day 1 (pre-dose) through 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.
Virology analysis set (TLOVR50 failures) included all participants who meet the TLOVR50 failure definition. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure and ‘n’ signifies participants evaluable for this measure at specified time point for each group, respectively.

Reporting Groups
  Description
Lersivirine 500 mg Two lersivirine 250 milligram (mg) tablets (equivalent to lersivirine 500 mg), a placebo tablet matched to lersivirine and a placebo tablet matched to efavirenz orally once daily along with tenofovir disoproxil fumarate (DF) 300 mg tablet and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in pharmacokinetic (PK) substudy switched to lersivirine morning dosing regimen, received 2 Lersivirine 250 mg tablets, a placebo tablet matched to lersivirine orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.
Lersivirine 750 mg Three Lersivirine 250 mg tablets (equivalent to lersivirine 750 mg) and a placebo tablet matched to efavirenz orally once daily along with tenofovir DF 300 mg and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in PK substudy switched to morning dosing regimen, received 3 Lersivirine 250 mg tablets orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.
Efavirenz 600 mg Three placebo tablets matched to lersivirine, efavirenz 600 mg tablet orally once daily along with tenofovir DF 300 mg and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in PK substudy switched to morning dosing regimen, received 3 placebo tablets matched to lersivirine and efavirenz 600 mg tablet orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. Efavirenz 600 mg tablet, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.

Measured Values
    Lersivirine 500 mg     Lersivirine 750 mg     Efavirenz 600 mg  
Number of Participants Analyzed  
[units: participants]
  5     8     6  
Number of Participants With NRTI and NNRTI Resistance-Associated Mutations (RAMs) at Time of Treatment Failure Through Week 24, 48 and 96  
[units: participants]
     
Week 24 (n=3, 4, 2)     3     0     1  
Week 48 (n=4, 3, 3)     3     1     1  
Week 96 (n= 5, 8, 6)     3     1     1  

No statistical analysis provided for Number of Participants With NRTI and NNRTI Resistance-Associated Mutations (RAMs) at Time of Treatment Failure Through Week 24, 48 and 96



10.  Secondary:   Number of Participants With Laboratory Test Abnormalities   [ Time Frame: Baseline up to Week 96 or early termination ]

Measure Type Secondary
Measure Title Number of Participants With Laboratory Test Abnormalities
Measure Description Laboratory analysis included hematology, blood chemistry, serum and urine pregnancy test, hepatitis testing and urinalysis. Laboratory values that met the criteria of the Division of Acquired Immuno Deficiency Syndrome (DAIDS) grade 1 (mild, symptoms causing no or minimal interference with usual social and functional activities) or greater were considered as abnormal.
Time Frame Baseline up to Week 96 or early termination  
Safety Issue Yes  

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.
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.

Reporting Groups
  Description
Lersivirine 500 mg Two lersivirine 250 milligram (mg) tablets (equivalent to lersivirine 500 mg), a placebo tablet matched to lersivirine and a placebo tablet matched to efavirenz orally once daily along with tenofovir disoproxil fumarate (DF) 300 mg tablet and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in pharmacokinetic (PK) substudy switched to lersivirine morning dosing regimen, received 2 Lersivirine 250 mg tablets, a placebo tablet matched to lersivirine orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.
Lersivirine 750 mg Three Lersivirine 250 mg tablets (equivalent to lersivirine 750 mg) and a placebo tablet matched to efavirenz orally once daily along with tenofovir DF 300 mg and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in PK substudy switched to morning dosing regimen, received 3 Lersivirine 250 mg tablets orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.
Efavirenz 600 mg Three placebo tablets matched to lersivirine, efavirenz 600 mg tablet orally once daily along with tenofovir DF 300 mg and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in PK substudy switched to morning dosing regimen, received 3 placebo tablets matched to lersivirine and efavirenz 600 mg tablet orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. Efavirenz 600 mg tablet, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.

Measured Values
    Lersivirine 500 mg     Lersivirine 750 mg     Efavirenz 600 mg  
Number of Participants Analyzed  
[units: participants]
  64     65     63  
Number of Participants With Laboratory Test Abnormalities  
[units: participants]
  59     58     57  

No statistical analysis provided for Number of Participants With Laboratory Test Abnormalities



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

Measure Type Secondary
Measure Title Lersivirine Success Percentage With Reference to Median Minimum Observed Plasma Concentration (Cmin)
Measure Description 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.
Time Frame Week 2, 4, 8, 12, 16, 24, 32, 40, 48  
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.
Due to the sparsity of the data, it was deemed that the interpretation of the pharmacokinetic/pharmacodynamic (PK/PD) results would be questionable, thus data was not analyzed.

Reporting Groups
  Description
Lersivirine 500 mg Two lersivirine 250 milligram (mg) tablets (equivalent to lersivirine 500 mg), a placebo tablet matched to lersivirine and a placebo tablet matched to efavirenz orally once daily along with tenofovir disoproxil fumarate (DF) 300 mg tablet and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in pharmacokinetic (PK) substudy switched to lersivirine morning dosing regimen, received 2 Lersivirine 250 mg tablets, a placebo tablet matched to lersivirine orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.
Lersivirine 750 mg Three Lersivirine 250 mg tablets (equivalent to lersivirine 750 mg) and a placebo tablet matched to efavirenz orally once daily along with tenofovir DF 300 mg and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in PK substudy switched to morning dosing regimen, received 3 Lersivirine 250 mg tablets orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.
Efavirenz 600 mg Three placebo tablets matched to lersivirine, efavirenz 600 mg tablet orally once daily along with tenofovir DF 300 mg and emtricitabine 200 mg tablet orally once daily, in the evening up to 96 weeks. Participants enrolled in PK substudy switched to morning dosing regimen, received 3 placebo tablets matched to lersivirine and efavirenz 600 mg tablet orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. Efavirenz 600 mg tablet, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet were continued in the evening in PK substudy. Evening dosing was continued for the remainder of the study up to Week 96.

Measured Values
    Lersivirine 500 mg     Lersivirine 750 mg     Efavirenz 600 mg  
Number of Participants Analyzed  
[units: participants]
  0     0     0  
Lersivirine Success Percentage With Reference to Median Minimum Observed Plasma Concentration (Cmin)              

No statistical analysis provided for Lersivirine Success Percentage With Reference to Median Minimum Observed Plasma Concentration (Cmin)



12.  Secondary:   Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24]) of Lersivirine   [ Time Frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 24 hours (hrs) post-dose on Week 4 ]

Measure Type Secondary
Measure Title Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24]) of Lersivirine
Measure Description AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours post-dose (0-24). Only participants from Lersivirine treatment arms were planned to be analyzed for Pharmacokinetic (PK) sub-study.
Time Frame 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 24 hours (hrs) post-dose on Week 4  
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.
Pharmacokinetic sub-study analysis set (PKSSAS) included all randomized Lersivirine participants who consented to participate in the PK sub-study, received the study medication on the day of the PK sub-study and had sufficient PK data for analysis.

Reporting Groups
  Description
Lersivirine 500 mg Participants enrolled in PK substudy received 2 Lersivirine 250 mg tablets and a placebo tablet matched to lersivirine orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet orally once daily were continued in the evening in PK substudy.
Lersivirine 750 mg Participants enrolled in PK substudy received 3 Lersivirine 250 mg tablets orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet orally once daily were continued in the evening in PK substudy.

Measured Values
    Lersivirine 500 mg     Lersivirine 750 mg  
Number of Participants Analyzed  
[units: participants]
  7     6  
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24]) of Lersivirine  
[units: nanogram*hour/milliliter (ng*hr/mL)]
Geometric Mean ( Geometric Coefficient of Variation )
  6002  
  ( 30% )  
  8677  
  ( 21% )  

No statistical analysis provided for Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24]) of Lersivirine



13.  Secondary:   Maximum Observed Plasma Concentration (Cmax) of Lersivirine   [ Time Frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 24 hrs post-dose on Week 4 ]

Measure Type Secondary
Measure Title Maximum Observed Plasma Concentration (Cmax) of Lersivirine
Measure Description No text entered.
Time Frame 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 24 hrs post-dose on Week 4  
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.
PKSSAS included all randomized Lersivirine participants who consented to participate in the PK sub-study, received the study medication on the day of the PK sub-study and had sufficient PK data for analysis.

Reporting Groups
  Description
Lersivirine 500 mg Participants enrolled in PK substudy received 2 Lersivirine 250 mg tablets and a placebo tablet matched to lersivirine orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet orally once daily were continued in the evening in PK substudy.
Lersivirine 750 mg Participants enrolled in PK substudy received 3 Lersivirine 250 mg tablets orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet orally once daily were continued in the evening in PK substudy.

Measured Values
    Lersivirine 500 mg     Lersivirine 750 mg  
Number of Participants Analyzed  
[units: participants]
  7     6  
Maximum Observed Plasma Concentration (Cmax) of Lersivirine  
[units: ng/mL]
Geometric Mean ( Geometric Coefficient of Variation )
  1056  
  ( 41% )  
  1354  
  ( 31% )  

No statistical analysis provided for Maximum Observed Plasma Concentration (Cmax) of Lersivirine



14.  Secondary:   Time to Reach Maximum Observed Plasma Concentration (Tmax) of Lersivirine   [ Time Frame: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 24 hrs post-dose on Week 4 ]

Measure Type Secondary
Measure Title Time to Reach Maximum Observed Plasma Concentration (Tmax) of Lersivirine
Measure Description No text entered.
Time Frame 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 24 hrs post-dose on Week 4  
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.
PKSSAS included all randomized Lersivirine participants who consented to participate in the PK sub-study, received the study medication on the day of the PK sub-study and had sufficient PK data for analysis.

Reporting Groups
  Description
Lersivirine 500 mg Participants enrolled in PK substudy received 2 Lersivirine 250 mg tablets and a placebo tablet matched to lersivirine orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet orally once daily were continued in the evening in PK substudy.
Lersivirine 750 mg Participants enrolled in PK substudy received 3 Lersivirine 250 mg tablets orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet orally once daily were continued in the evening in PK substudy.

Measured Values
    Lersivirine 500 mg     Lersivirine 750 mg  
Number of Participants Analyzed  
[units: participants]
  7     6  
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Lersivirine  
[units: hr]
Median ( Full Range )
  1.00  
  ( 0.483 to 2.00 )  
  2.00  
  ( 0.500 to 8.00 )  

No statistical analysis provided for Time to Reach Maximum Observed Plasma Concentration (Tmax) of Lersivirine



15.  Secondary:   Plasma Concentration of Lersivirine at 24 Hour   [ Time Frame: 24 hrs post-dose on Week 4 ]

Measure Type Secondary
Measure Title Plasma Concentration of Lersivirine at 24 Hour
Measure Description The observed plasma concentration at 24 hours post-dose (C 24h).
Time Frame 24 hrs post-dose on Week 4  
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.
PKSSAS included all randomized Lersivirine participants who further consented to participate in the PK sub-study, received the study medication on the day of the PK sub-study and had sufficient PK data for analysis.

Reporting Groups
  Description
Lersivirine 500 mg Participants enrolled in PK substudy received 2 Lersivirine 250 mg tablets and a placebo tablet matched to lersivirine orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet orally once daily were continued in the evening in PK substudy.
Lersivirine 750 mg Participants enrolled in PK substudy received 3 Lersivirine 250 mg tablets orally once daily in the morning for 7 days prior to Week 4, and in the morning and evening on 1 day following Week 4. A placebo tablet matched to efavirenz, tenofovir DF 300 mg tablet and emtricitabine 200 mg tablet orally once daily were continued in the evening in PK substudy.

Measured Values
    Lersivirine 500 mg     Lersivirine 750 mg  
Number of Participants Analyzed  
[units: participants]
  7     6  
Plasma Concentration of Lersivirine at 24 Hour  
[units: ng/mL]
Geometric Mean ( Geometric Coefficient of Variation )
  49.56  
  ( 73% )  
  57.70  
  ( 34% )  

No statistical analysis provided for Plasma Concentration of Lersivirine at 24 Hour



16.  Secondary:   Population Pharmacokinetic (PK) of Lersivirine   [ Time Frame: Week 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
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