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 ]

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 ]

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 ]
  Hide Outcome Measure 3

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 ]

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 ]

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 ]

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 ]

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 ]

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 ]

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

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 ]

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 ]

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 ]

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 ]

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

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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