Intelence (Etravirine) - Summary

INTELENCE SUMMARY

INTELENCE™ (etravirine) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) of human immunodeficiency virus type 1 (HIV-1).

INTELENCE™ [Trademark of Tibotec Pharmaceuticals Ltd.] , in combination with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-experienced adult patients, who have evidence of viral replication and HIV-1 strains resistant to a non-nucleoside reverse transcriptase inhibitor (NNRTI) and other antiretroviral agents.

This indication is based on Week 24 analyses from 2 randomized, double-blind, placebo-controlled trials of INTELENCE™. Both studies were conducted in clinically advanced, 3-class antiretroviral (NNRTI, N[t]RTI, PI) treatment-experienced adults.

The following points should be considered when initiating therapy with INTELENCE™:

• Treatment history and, when available, resistance testing, should guide the use of INTELENCE™.
• The use of other active antiretroviral agents with INTELENCE™ is associated with an increased likelihood of treatment response.
• In patients who have experienced virologic failure on an NNRTI-containing regimen, do not use INTELENCE™ in combination with only N[t]RTIs [ see Clinical Studies ].
• The risks and benefits of INTELENCE™ have not been established in pediatric patients or in treatment-naïve adult patients.

NEWS HIGHLIGHTS

Published Studies Related to Intelence (Etravirine)

Etravirine: a second-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) active against NNRTI-resistant strains of HIV. [2009.04]
BACKGROUND: Since 1981, the AIDs epidemic has continued to expand and, at the end of 2007, there were ~33 million people worldwide living with HIV, including 1.2 million in North America. OBJECTIVE: This article provides a comprehensive overview of the nonnucleoside reverse transcriptase inhibitor (NNRTI) etravirine when used in treatment-experienced adult patients with multidrug-resistant HIV infections... CONCLUSION: Etravirine is an NNRTI that was reported to be effective when used as part of an optimized, highly active antiretroviral therapy regimen in NNRTI treatment-experienced adult patients with HIV.

Impact of reverse transcriptase resistance on the efficacy of TMC125 (etravirine) with two nucleoside reverse transcriptase inhibitors in protease inhibitor-naive, nonnucleoside reverse transcriptase inhibitor-experienced patients: study TMC125-C227. [2008.11]
OBJECTIVES: TMC125-C227, an exploratory phase II, randomized, controlled, open-label trial, compared the efficacy and safety of TMC125 (etravirine) with an investigator-selected protease inhibitor (PI) in nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant, protease inhibitor-naive, HIV-1-infected patients... CONCLUSIONS: In a PI-naive population, with baseline NRTI and NNRTI resistance and NRTI recycling, TMC125 was not as effective as first use of a PI. Therefore the use of TMC125 plus NRTIs alone may not be optimal in PI-naive patients with first-line virological failure on an NNRTI-based regimen. Baseline two-class resistance, rather than pharmacokinetics or other factors, was the most likely reason for suboptimal responses.

Safety, tolerability, and preliminary efficacy of 48 weeks of etravirine therapy in a phase IIb dose-ranging study involving treatment-experienced patients with HIV-1 infection. [2008.10.01]
BACKGROUND: Etravirine (ETR; also known as TMC125) is a new nonnucleoside reverse-transcriptase inhibitor with activity against wild-type and nonnucleoside reverse-transcriptase inhibitor-resistant human immunodeficiency virus type 1 (HIV-1)... CONCLUSIONS: ETR was generally safe and well tolerated during long-term administration in treatment-experienced, HIV-1-infected patients, and it had a safety profile comparable to that of placebo.

Impact of reverse transcriptase resistance on the efficacy of TMC125 (etravirine) with two nucleoside reverse transcriptase inhibitors in protease inhibitor-naive, nonnucleoside reverse transcriptase inhibitor-experienced patients: study TMC125-C227. [2008.09.14]
Objectives TMC125-C227, an exploratory phase II, randomized, controlled, open-label trial, compared the efficacy and safety of TMC125 (etravirine) with an investigator-selected protease inhibitor (PI) in nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant, protease inhibitor-naive, HIV-1-infected patients...

Etravirine has no effect on QT and corrected QT interval in HIV-negative volunteers. [2008.06]
BACKGROUND: Etravirine (TMC125), a next-generation nonnucleoside reverse transcriptase inhibitor, has shown antiviral efficacy in 2 large Phase 3 trials. In vitro and in vivo studies have shown that etravirine is not associated with proarrhythmic potential. Electrocardiograms (ECGs) from healthy and HIV 1-infected volunteers showed no clinically relevant changes. OBJECTIVE: To evaluate the effect of 2 etravirine dosing regimens on QT/corrected QT interval (QTc) in HIV-negative volunteers and assess pharmacokinetic and additional safety parameters... CONCLUSIONS: Etravirine does not prolong the QTc interval. No clinically relevant ECG changes were observed in HIV-negative volunteers. Short-term dosing of etravirine in HIV-negative volunteers was generally safe and well tolerated.

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Clinical Trials Related to Intelence (Etravirine)

TMC125-C229: TMC125 in HIV-1 Infected Subjects, Who Were Randomized to a TMC125 Treatment Arm in a Sponsor Selected TMC125 Trial and Were Treated for at Least 48 Weeks [Recruiting]
This is a Phase II, open-label, roll-over trial to evaluate the long-term safety and tolerability of TMC125, administered as part of an individually optimized antiretroviral therapy (ART), in HIV-1 infected subjects. In addition, the antiviral activity and immunologic effect of TMC125 as part of an ART over time, and the genotypic and phenotypic changes over time will be evaluated.

Evaluating Once Daily Etravirine in Treatment-Naive Adults With HIV Infection [Not yet recruiting]
The main study is a single arm, open-label, prospective study to assess antiretroviral activity and tolerability of etravirine (TMC-125) 400 mg once daily, given with fixed-dose tenofovir/emtricitabine, in treatment-naïve HIV-1-infected men and women. There are also a genital secretions pharmacokinetic (PK) sub-study and a metabolic sub-study. The purpose of the genital secretions PK sub-study is to gain information about drug levels and HIV-1 RNA in genital secretions when subjects are taking etravirine. The purpose of the metabolic sub-study is to learn about the effects of etravirine on body composition, as well as lipid and glucose levels.

An Open-Label Trial With TMC125 in Patients Who Have Virologically Failed in a DUET Trial (TMC125-C206 or TMC125-C216). [Recruiting]
The purpose of this trial is to evaluate the long-term safety and tolerability of TMC125 200 mg twice daily as part of an antiretroviral therapy including TMC114/rtv and an investigator selected optimized background in HIV-1 infected patients who have participated in a DUET trial (TMC125-C206 or TMC125 C216) and have met the definition of virologic failure at Week 24 or later in these trials.

A Study to Assess the Pharmacokinetics (Blood Levels) of TMC114 (Darunavir) Taken With TMC114r (Ritonavir), and TMC125 (Etravirine) in HIV-1 Infected Pregnant Women [Recruiting]
The purpose of this study is to look at how changes in the body during pregnancy may change the effectiveness of TMC114 (darunavir) and TMC114r (ritonavir) taken together and TMC125 (etravirine) taken alone or with darunavir and ritonavir in patients with human immunodeficiency virus-1 (HIV-1). This study will look at how these drugs are absorbed in the body, how they are distributed within the body and how they are removed from the body over time. Any pregnant woman who is currently receiving darunavir with ritonavir and/or etravirine for HIV-1, and who meets the eligibility criteria for the study, will be allowed to enroll. Patients must be willing to remain on study medication during the course of their pregnancy, and 12 weeks postpartum. The information collected may help answer questions about how to best prescribe these three drugs for pregnant women.

TMC125-TiDP2-C188: A Phase I, Open-label Trial to Investigate the Pharmacokinetic Effect of Multiple-dose TMC125 on Buprenorphine and Norbuprenorphine Administered in HIV-negative Patients on Stable Buprenorphine/Naloxone Maintenance Therapy. [Recruiting]
TMC125 is from the class of drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs). NNRTIs work by blocking reverse transcriptase, a protein that HIV needs to make more copies of itself. TMC125 is used in the treatment of adults with HIV-1 infection. The purpose of this trial is to see if there is any potential interaction (change in the effectiveness of the drug) when taking multiple-dose TMC125 and buprenorphine/naloxone together. The trial will also assess the short-term safety and tolerability (how well your body handles the drug) when TMC125 and buprenorphine/naloxone are taken together.

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