A Long Term Safety Study Of Lersivirine For The Treatment Of HIV-1 Infection In Subjects Who Have Completed Treatment With Lersivirine In Studies A5271015 And A5271022

Study Overview
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Brief Summary
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This is a study to assess long-term safety and efficacy of lersivirine in patients who have completed 96 weeks of treatment with lersivirine in studies A5271015 and A5271022.

Detailed Description
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The trial was terminated prematurely on January 29, 2013, due to the decision of the sponsor to discontinue development of lersivirine. The decision to terminate the trial was not based on any safety or efficacy concerns.

Official Title
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A Long Term Open-Label Extension Study Of Lersivirine For The Treatment Of HIV-1 Infection

Conditions
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HIV-1

Intervention / Treatment
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* Drug: lersivirine
* Drug: lersivirine
* Drug: efavirenz
* Drug: lersivirine
* Drug: lersivirine
* Drug: etravirine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must complete of 96 weeks of treatment with lersivirine (or comparator where required by local regulation) in one of the parent protocols (A5271015 or A5271022). Patients must have had a viral load less than 50 copies/mL at Week 84 of the parent protocol. For women who can have children, a negative urine pregnancy test at the Day 1 visit. Exclusion Criteria: Patients with any Grade 4 Division of AIDS toxicity (except for lipids and asymptomatic glucose elevations will not be included in this trial. Patients being treated with another investigational product or in another clinical trial, except the lersivirine parent protocols will not be included in this trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LRV 500mg<br> | Drug: lersivirine<br>* Lersivirine 500 mg tablets PO taken once daily + tenofovir DF 300 mg/emtricitabine 200 mg tablets PO once daily<br>|
| Experimental: LRV 750mg +TVD<br> | Drug: lersivirine<br>* Lersivirine 750 mg tablets PO taken once daily + tenofovir DF 300 mg/emtricitabine 200 mg tablets PO once daily<br>|
| Active Comparator: EFV<br> | Drug: efavirenz<br>* Efavirenz 600 mg tablets PO taken once daily + tenofovir DF 300 mg/emtricitabine 200 mg tablets PO once daily<br>|
| Experimental: LRV 750mg+ DRV/r + OBT<br> | Drug: lersivirine<br>* Lersivirine 750 mg tablets PO taken once daily + darunavir 600 mg tablets/ritonavir 100 mg tablets or capsules PO taken twice daily + 1 optimized NRTI<br>|
| Experimental: LRV 1000mg +DRV/r + OBT<br> | Drug: lersivirine<br>* Lersivirine 1000 mg PO tablets + darunavir 600 mg tablets/ritonavir 100 mg tablets or capsules PO taken twice daily + 1 optimized NRTI<br>|
| Active Comparator: ETR<br> | Drug: etravirine<br>* Etravirine 200 mg PO tablets + darunavir 600 mg tablets/ritonavir 100 mg tablets or capsules taken twice daily + 1 optimized NRTI<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Plasma Human Immunodeficiency Virus - 1 (HIV-1) Ribonucleic Acid (RNA) Level <50 Copies/mL at 144 Weeks From Day 1 of the Parent Protocol | Number of participants with HIV-1 RNA level <50 copies/mL plasma was summarized at 48 weeks i.e. 144 weeks from Day 1 of the parent protocol. Roche Amplicor HIV-1 Monitor assay was used to measure the HIV-1 RNA level. | 144 Weeks from Day 1 of the parent protocol | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Plasma HIV-1 RNA Level <50 Copies/mL up to Week 208 | Number of participants with HIV-1 RNA level <50 copies/mL plasma was summarized at last visit. Abbott RealTime HIV-1 assay was used to measure the HIV-1 RNA level. | Up to Week 208 | 
| Change From Baseline in CD4+ Lymphocyte Counts (Absolute) at 144 Weeks From Day 1 of the Parent Protocol | Participant's immunological status assessed by CD4+ lymphocyte count (absolute and percentage) at 48 weeks (ie, 144 weeks from Day 1 of the parent protocol) | 144 Weeks from Day 1 of the parent protocol | 
| Change From Baseline in CD4+ Lymphocyte Counts (Percentage) at 144 Weeks From Day 1 of the Parent Protocol | Participant's immunological status assessed by CD4+ lymphocyte count (absolute and percentage) at 48 weeks (ie, 144 weeks from Day 1 of the parent protocol) | 144 Weeks from Day 1 of the parent protocol | 
| Change From Baseline in CD4+ Lymphocyte Counts (Absolute) at 192 Weeks From Day 1 of the Parent Protocol | Participant's immunological status assessed by CD4+ lymphocyte count (absolute and percentage) at 192 weeks from Day 1 of the parent protocol. | 192 Weeks from Day 1 of the parent protocol | 
| Change From Baseline in CD4+ Lymphocyte Counts (Percentage) at 192 Weeks From Day 1 of the Parent Protocol | Participant's immunological status assessed by CD4+ lymphocyte count (absolute and percentage) at 192 weeks from Day 1 of the parent protocol. | 192 Weeks from Day 1 of the parent protocol | 
| Virology Analysis Participant Accountability From Week 96 Through Study Termination | Virology analysis included virus susceptibility (phenotype and genotype)to a standard panel of approved antiretrovirals as determined by the Monogram Biosciences PhenoSense GT assay. Below analysis table included the following parameters: 1. protocol-defined treatment failure was defined as an increase in HIV-1 RNA to detectable levels (≥50 copies/mL) on 2 consecutive measurements, the second measurement taken no more than 14 days after the first measurement); 2. Treatment failure: treatment failure (both virologic and non-virologic) was defined as a subject who met the protocol-defined treatment failure criterion or discontinued from the study; 3. NRTI or NNRTI resistance mutations: nucleoside reverse transcriptase inhibitor or lersivirine-associated resistance-associated mutations (RAM) based on the International AIDS Society-USA (IAS-USA) RAM guidelines; 4. 'with result' meant an analyzed sample returned genotypic result or phenotypic result or both. | Week 96 through study termination |