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

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

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.

Study Overview

• Status: Terminated
• Conditions: HIV-1
• Intervention / Treatment: Drug: lersivirine; Drug: lersivirine; Drug: lersivirine; Drug: lersivirine; Drug: efavirenz; Drug: etravirine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Pfizer Investigational Site
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Pfizer Investigational Site
• Brazil
  • RJ
    • Nova Iguacu, RJ, Brazil, 26030-381
      • Pfizer Investigational Site
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1K2
      • Pfizer Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H2L 4P9
      • Pfizer Investigational Site
    • Montreal, Quebec, Canada, H2L 5B1
      • Pfizer Investigational Site
• Italy
  • Milano, Italy, 20127
    • Pfizer Investigational Site
  • Torino, Italy, 10149
    • Pfizer Investigational Site
• Mexico
  • Distrito Federal
    • Mexico, Distrito Federal, Mexico, 14050
      • Pfizer Investigational Site
• Poland
  • Bydgoszcz, Poland, 85-030
    • Pfizer Investigational Site
  • Warszawa, Poland, 01-201
    • Pfizer Investigational Site
• South Africa
  • Pretoria, South Africa, 0083
    • Pfizer Investigational Site
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2193
      • Pfizer Investigational Site
    • Pretoria, Gauteng, South Africa, 0083
      • Pfizer Investigational Site
    • Soweto, Gauteng, South Africa, 2013
      • Pfizer Investigational Site
  • Kwazulu-Natal
    • Durban, Kwazulu-Natal, South Africa, 4001
      • Pfizer Investigational Site
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7925
      • Pfizer Investigational Site
• Switzerland
  • Lugano, Switzerland, 6903
    • Pfizer Investigational Site
  • St. Gallen, Switzerland, 9007
    • Pfizer Investigational Site
  • Zuerich, Switzerland, 8091
    • Pfizer Investigational Site
• United Kingdom
  • London, United Kingdom, NW3 2QG
    • Pfizer Investigational Site
  • London, United Kingdom, SW10 9NH
    • Pfizer Investigational Site
  • East Sussex
    • Brighton, East Sussex, United Kingdom, BN2 1ES
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: ViiV Healthcare

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: December 3, 2010
• First Submitted That Met QC Criteria: December 3, 2010
• First Posted (Estimate): December 6, 2010

Study Record Updates

• Last Update Posted (Estimate): June 9, 2014
• Last Update Submitted That Met QC Criteria: May 27, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Etravirine; Efavirenz
• Other Study ID Numbers: A5271037