TMC125IFD3002 - The VIOLIN Study: to EValuate Etravirine TolerabIlity, PharmacOkinetics With Other AntiretroviraLs In TreatmeNt Experienced Patients

Condition(s) targeted: HIV

Intervention: etravirine (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Tibotec Pharmaceuticals, Ireland

Official(s) and/or principal investigator(s):
Tibotec Pharmaceuticals Clinical Trial, Study Director, Affiliation: Tibotec Pharmaceutical Limited

Overall contact:
Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions:, Email: JNJ.CT@sylogent.com

The purpose of this study is to learn more about the safety and tolerability of a drug called Intelence (also known as etravirine or ETR). ETR is a type of non-nucleoside reverse transcriptase inhibitor (NNRTI) which has shown high activity against wild type Human immunodeficiency virus (HIV-1), and HIV strains resistant to other NNs. ETR has been approved by the US Food and Drug Administration (FDA), European Medicines Agency (EMEA) and other regulatory authorities in Canada, South America and Asia for the treatment of Human Immunodeficiency Virus (HIV-1).

Official title: An Open-Label Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Etravirine (ETR) in Combination With Other Antiretrovirals (ARVs) in Antiretroviral Treatment-Experienced HIV-1 Infected Subjects

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Proportion of subjects with an adverse event

AUC12h and C0h of ETR by CYP2C9 or CYP2C19 genotype

Secondary outcome:

Proportion of subjects with virologic suppression (HIV-1 RNA <50 copies/mL) at Week 48

Changes in CD4 cell count over time

Changes in viral genotype/phenotype over time

Detailed description: This is an open-label (all people involved know the identity of the intervention), single arm, multicenter Phase IV study to evaluate the safety, tolerability, and pharmacokinetics of etravirine (ETR) in combination with antiretroviral therapy (ARVs) other than darunavir (DRV) + ritonavir (rtv). In addition, antiviral activity and the pharmacokinetic/pharmacodynamic relationship, the amounts of a drug in your blood, for safety of ETR will be assessed. The study will consist of a screening period of maximum 6 weeks, a baseline visit and a 48-week treatment period. After the end of the treatment period, patients with ongoing adverse events (AEs) will be followed for an additional 4 weeks. At least 200 ARV treatment-experienced Human immunodeficiency virus (HIV-1) infected patients will be enrolled in this study. Patients will be considered ARV treatment-experienced if they have been on their current stable highly active antiretroviral therapy (HAART) regimen for at least 8 weeks prior to screening. The study population will consist of patients who need to change their current HAART regimen due to any of the following reasons: (1) patients experiencing virologic failure (with a screening viral load value = 500 HIV-1 RNA copies/mL) or (2) patients switching due to simplification of their current regimen or due to AEs and/or tolerability reasons (with a screening viral load value < 50 HIV-1 RNA copies/mL). Patients will receive ETR 200 mg twice daily (b. i.d.) in combination with an investigator-selected background regimen. In addition to ETR, which needs to be active based on resistance testing, the background regimen should consist of at least 1 active ARV resulting in a treatment regimen with at least 2 active ARVs. The following exceptions to this are: (1) if raltegravir (RAL) or atazanavir/ritonavir (ATV/rtv) are part of the background regimen, the number of active ARVs in this background regimen should be at least 2; (2) low-dose ritonavir should not be counted as an active ARV. DRV/rtv will not be allowed in the background regimen in order to evaluate the safety and pharmacokinetics of ETR in combination with ARVs other than DRV/rtv. Furthermore, a background regimen consisting of nucleoside transcriptase inhibitors (NRTIs) only will not be allowed. The background regimen cannot be modified until the end of the treatment period with the following exception: switches within the ARV class will be allowed for well documented tolerability/toxicity reasons. For patients who, in the opinion of the investigator, are deriving clinical benefit from ETR, and to whom ETR is not commercially available in his/her country, is not reimbursed or cannot be accessed from another source (e. g. access program, government program) in the region the patient is living in, the possibility to extend their ETR treatment period will be provided. For each subject, the optional extension will immediately follow the 48-week treatment period and will continue until virologic failure, treatment limiting toxicity, patients lost to follow-up, patient's withdrawal, pregnancy or when ETR has become commercially available to the patient n his/her country. The etravirine tablets (100/200 mg) are to be taken orally twice daily after a meal. A total daily dose of 400 mg is to be taken for 48 weeks.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Have not changed your drugs to treat HIV for 8 weeks and currently experiencing

virologic failure, (viral load value = 500 HIV 1 RNA copies /mL)

- or switching due to simplification of their regimen or due to adverse event or

tolerability reasons, (viral load value <50 HIV 1 RNA copies /mL). You much not have demonstrated sensitivity to ETR and to at least 1 ARV in the background regimen, based on the resistance test at screening or resistance history or have previously received treatment with ETR. You must agree not to have unprotected sex while on the study. You must not have a currently active AIDS defining illness. You must not take any non-ARV investigational agents within 90 days prior to screening. You must not use of any drugs or other therapies that your doctirs tell you are disallowed. Your doctor must check that your liver is functioning correctly. Any disease that in your study doctor's opinion, would compromise the subject's safety. Exclusion Criteria:

- Any currently active illness or toxicity due to your HIV infection

Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions:, Email: JNJ.CT@sylogent.com

Buenos Aires, Argentina; Not yet recruiting

Buenos Aires N/A, Argentina; Withdrawn

Mar Del Plata N/A, Argentina; Not yet recruiting

Neuquen, Argentina; Withdrawn

Rosario, Argentina; Not yet recruiting

Bobigny, France; Not yet recruiting

Lyon, France; Not yet recruiting

Nantes, France; Not yet recruiting

Nice, France; Not yet recruiting

Paris, France; Not yet recruiting

Paris Cedex 12, France; Withdrawn

Paris Cedex 15, France; Withdrawn

Guatemala, Guatemala; Not yet recruiting

Guatemala, Guatemala; Withdrawn

Bangalore, India; Not yet recruiting

Bangalore, India; Withdrawn

Byculla, India; Withdrawn

Hyderabad, India; Not yet recruiting

Hyderabad Andh Prad, India; Not yet recruiting

Lucknow, India; Not yet recruiting

Mangalore, India; Not yet recruiting

Manipal, India; Not yet recruiting

Mumbai, India; Withdrawn

Mumbai, India; Not yet recruiting

Mysore, India; Withdrawn

Navrangpura, India; Not yet recruiting

Taramani, India; Withdrawn

Vadodara, India; Not yet recruiting

Varanasi, India; Withdrawn

Aguascalientes, Mexico; Not yet recruiting

Ciudad De Mexico, Mexico; Withdrawn

Culiacán, Mexico; Not yet recruiting

Estado De México, Mexico; Not yet recruiting

Guadalajara, Mexico; Not yet recruiting

Mexico, Mexico; Not yet recruiting

Mexico D.F., Mexico; Not yet recruiting

Monterrey, Mexico; Withdrawn

San Luis Potosi, Mexico; Not yet recruiting

San Luis Potosi, Mexico; Withdrawn

Zapopan, Mexico; Withdrawn

Iquitos, Peru; Not yet recruiting

Lima, Peru; Not yet recruiting

San Juan, Puerto Rico; Recruiting

Bucharest, Romania; Not yet recruiting

Bucuresti, Romania; Withdrawn

Constanta, Romania; Not yet recruiting

Craiova, Romania; Not yet recruiting

Suceava, Romania; Not yet recruiting

Timisoara, Romania; Not yet recruiting

Krasnodar, Russian Federation; Not yet recruiting

Moscow, Russian Federation; Withdrawn

Moscow N/A, Russian Federation; Not yet recruiting

Saint-Petersburg, Russian Federation; Not yet recruiting

Sint Petersburg, Russian Federation; Not yet recruiting

Volgograd, Russian Federation; Not yet recruiting

Voronezh, Russian Federation; Not yet recruiting

Bloemfontein, South Africa; Not yet recruiting

Boksburg, South Africa; Not yet recruiting

Cape Town, South Africa; Withdrawn

Dundee, South Africa; Not yet recruiting

Durban N/A, South Africa; Not yet recruiting

Johannesburg, South Africa; Not yet recruiting

Johannesburg, South Africa; Withdrawn

Newtown, South Africa; Not yet recruiting

Port Elizabeth, South Africa; Not yet recruiting

Pretoria, South Africa; Not yet recruiting

Pretoria N/A, South Africa; Not yet recruiting

Westdene Johannesburg Gauteng, South Africa; Not yet recruiting

Beresina Village, Vinnitsya Region, Ukraine; Not yet recruiting

Donetsk, Ukraine; Not yet recruiting

Kharkiv, Ukraine; Not yet recruiting

Kyiv, Ukraine; Not yet recruiting

Lugansk, Ukraine; Not yet recruiting

Lviv, Ukraine; Not yet recruiting

Odessa, Ukraine; Withdrawn

Sumy, Ukraine; Not yet recruiting

Vinnytsia, Ukraine; Not yet recruiting

Phoenix, Arizona, United States; Recruiting

Beverly Hills, California, United States; Recruiting

Burbank, California, United States; Recruiting

Denver, Colorado, United States; Withdrawn

Fort Laudersale, Florida, United States; Recruiting

Miami, Florida, United States; Recruiting

Miami, Florida, United States; Not yet recruiting

Orlando, Florida, United States; Withdrawn

Tamarac, Florida, United States; Withdrawn

Atlanta, Georgia, United States; Withdrawn

Baltimore, Maryland, United States; Withdrawn

Boston, Massachusetts, United States; Not yet recruiting

Springfield, Massachusetts, United States; Not yet recruiting

Saint Louis, Missouri, United States; Not yet recruiting

New York, New York, United States; Withdrawn

New Yrok, New York, United States; Withdrawn

Akron, Ohio, United States; Not yet recruiting

Akron, Ohio, United States; Withdrawn

Cincinnati, Ohio, United States; Withdrawn

Philadelphia, Pennsylvania, United States; Withdrawn

Longview, Texas, United States; Recruiting

To learn how to participate in this trial please click here.

Starting date: August 2011
Last updated: December 2, 2011